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Slide 1 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA
Slide 2 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders
Slide 3 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse
Slide 4 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions
Slide 5 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved!
Slide 6 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe
Slide 7 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending)
Slide 8 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal
Slide 9 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT
Slide 10 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity
Slide 11 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels
Slide 12 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders
Slide 13 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction
Slide 14 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR?
Slide 15 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167)
Slide 16 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction?
Slide 17 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That…
Slide 18 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND…
Slide 19 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging
Slide 20 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value
Slide 21 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs)
Slide 22 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001.
Slide 23 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions
Slide 24 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system
Slide 25 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning
Slide 26 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean???
Slide 27 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less
Slide 28 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less
Slide 29 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies
Slide 30 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability
Slide 31 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability
Slide 32 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?)
Slide 33 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What?
Slide 34 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48)
Slide 35 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment
Slide 36 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment
Slide 37 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine
Slide 38 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine
Slide 39 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders
Slide 40 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?)
Slide 41 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be:
Slide 42 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness
Slide 43 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness
Slide 44 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration
Slide 45 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block
Slide 46 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness
Slide 47 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders
Slide 48 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma
Slide 49 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor
Slide 50 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use?
Slide 51 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug?
Slide 52 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996
Slide 53 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30
Slide 54 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . .
Slide 55 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction
Slide 56 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities
Slide 57 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated
Slide 58 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express)
Slide 59 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated
Slide 60 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies
Slide 61 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated
Slide 62 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time
Slide 63 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated
Slide 64 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety
Slide 65 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone
Slide 66 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone Vmat transporter stimulation DA How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) vesicle Neuronal terminal
Slide 67 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone Vmat transporter stimulation DA How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) vesicle Neuronal terminal Psychostimulants
Slide 68 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone Vmat transporter stimulation DA How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) vesicle Neuronal terminal Psychostimulants Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated GABA and cannabinoid systems critical for function
Slide 69 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone Vmat transporter stimulation DA How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) vesicle Neuronal terminal Psychostimulants Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated GABA and cannabinoid systems critical for function Relieve stress-related drug abuse CRF antagonist Abstinence RELAPSE CRF Anxiety
Slide 70 - The Neurobiology of Drug Addiction Glen R. Hanson, Ph.D., D.D.S. Director, Utah Addiction Center Professor of Pharmacology and Toxicology, U of U Senior Advisor, NIDA Drug Abuse and Addiction are Among the Most Serious Public HealthProblems Facing Our Society and Frequently Coexist with Other Mental and Physical Disorders Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Two Decades of Neurobiological Research Have Brought Us A New Understanding of Drug Abuse and Addiction, Their Complexity and their Solutions We Know That Despite Their Many Differences, Virtually All Abused Substances Enhance Dopamine (neurotransmitter) Activity (particularly related to pleasure, motor, and cognitive function For Example… Other pathways also involved! Dopamine Pathways Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making Serotonin Pathways Functions mood memory processing sleep cognition nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe Neuronal structure (receiving) (sending) /serotonin Vmat transporter DA/5HT How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) marijuana (activate cannabinoid receptors) caffeine alcohol (activate GABA receptors; an inhibitory transmitter) Drug : cocaine ritalin vesicle Neuronal terminal Release DA from vesicles and reverse transporter Drug Types: Amphetamines -methamphetamine -MDMA (Ecstasy) Vmat transporter serotonin/ DA/5HT Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity Natural Rewards Elevate Dopamine Levels Implication: Elucidation of the mechanism of drug addiction will help to understand other addictive and motivational behaviors/disorders OFC SCC MOTIVATION/ DRIVE (saliency) Brain Circuits Involved in Drug Addiction HOW DOES ADDICTION OCCUR? Principles of Behavior Dynamics Behavior Tracts Compete for Expression Expression is Determined by (i) Dominance of Tracts, (ii) Strength of Prefrontal Cortex to Select, (iii) Relevance or saliency (orbitofrontal cortex) Activation of Dopamine reward pathway initiates a behavior track dopamine initiated (Miller & Cohen, Annu. Rev. Neurosci. 24 [2001] 167) Principles of Behavior Dynamics How does a behavior become an addiction? Prolonged Drug Use Changes the Brain and In Fundamental and Long-Lasting Ways We Have Generated A Lot of Evidence Showing That… We Have Evidence That These Changes Can Be Both Structural and Functional AND… Positron Emission Tomography BRAIN IMAGING Magnetic Resonance Imaging control cocaine abuser Decreases in Metabolism in Orbito Frontal Cortex (OFC) Volkow et al. Am. J. Psychiatry 148, 621 Compromise assigning appropriate Value Source: McCann U.D. et al., The Journal of Neuroscience, 18(20), pp. 8417-8422, October 15, 1998. METH Suppresses Expression of DAT (note: duration of use/3-20 yrs; abstinent/ 1-4 yrs) Comparison Subject METH Abuser Dopamine Transporter Loss After Heavy Methamphetamine Use (PET analysis) Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Dependence of Verbal Memory on Striatal DAT R = 0.70 p < 0.005 R = 0.64 p < 0.01 Interference recall Delayed recall Source: Volkow, N.D. et al., Am J. Psychiatry, 158(3), pp. 377-382, 2001. Compromises Cognitive Functions MOTOR FUNCTION Slowed gait Impaired balance Impairment correlates with damage to dopamine system Implication: Brain changes resulting from prolonged use of psychostimulants, such as methamphetamine may be reflected in compromised cognitive and motor functioning Is There Recovery? Good News: After 2 years some of the dopamine deficits are recovering Bad News: Functional deficits persist What does this mean??? Reward System in Addiction Cocaine Food Activity of Reward System METH Alcohol controls treated More Less INHERITED FACTORS (genetic vulnerability-not inevitability) Common strategy to investigate are Twin Studies In General: Inheritability for Drug Abuse Ranges From 40-60% Some Variability Between Drugs Some Gender Variability Complex genetics Complex phenotypes (expressions) (Relation to Risk Factors?) VULNERABILITY to What? For Example- Contribution of Genetic Factors to: Nicotine- Liability to initiate=56% Transition to dependence=70% Smoking persistence= >50% (Lerman & Berrettine, Amer. J. Med. Gen. 54 (2003) 48) Genetics May Influence How Neurobiology Interacts With Environment PET Images: Dopamine Receptor Density More likely to self- administer Cocaine Addictive Disorders Often Co-Exist with or Predispose to Mental Disorders (Note: can we have parity for mental health with- out considering drug abuse?) Common Underlying Neurobiological Factors Can Be: Because of this overlap, drugs of abuse can cause symptoms that mimic most forms of mental illness Some drugs of abuse have a mechanism of action similar to that of drugs used as psychotherapeutic agents Significance: rationale for self-administration Serotonin/dopamine synaptic terminal Synaptic vesicle Postsynaptic target transporter Prozac, Ritalin, & Cocaine block Chronic use of some of these drugs of abuse may alter the way the brain functions, making persons particularly susceptible to mental illness Double People With Comorbid Mental and Addictive Disorders Have a Brain Disease Double Mental Disorder Addictive Disorder Comorbid Disorders Role of Stress and Trauma The Stress Hormone Cycle Hypothalamus Pituitary Gland Adrenal Glands Kidneys CRF ACTH Stress Responses Stress Responses Stress Responses Stress Responses CRF: Corticotropin Releasing Factor DRUG USE(Self-Medication) STRESS CRF Anxiety CRF Anxiety What Role Does Stress Play In Initiating Drug Use? Abstinence RELAPSE CRF Anxiety What Happens When A Person Stops Taking A Drug? Stress Reliably Reinstates Drug Seeking in Rats Saline Nicotine Nicotine-trained rats Footshock Saline Cocaine Footshock Water Alcohol Footshock Cocaine-trained rats Alcohol-trained rats 0 20 40 60 80 100 Responses Inactive Lever Active Lever Saline Heroin Footshock Heroin-trained rats * * * * * * * * 0 20 40 60 80 100 Responses From: Psychopharmacology, 1996, 1998, 1999 ; J. Neurosci. 1996 CRF1 Receptor Antagonist Attenuates Stress-Induced Reinstatement of Drug Seeking Alcohol-trained rats From: Shaham et al. Psychopharmacology 1998; Le et al. Psychopharmacology, 2000 CP-154,526 Dose (mg/kg, SC) Intermittent Footshock No stress Heroin-trained rats Cocaine-trained rats 0 15 * 30 * 0 15 30 45 60 Responses (3 hr) * * 0 15 30 * 0 15 30 45 60 Responses (1 hr) 0 15 30 That was then . . . We Are Capitalizing on Basic Science Discoveries in the Design Of Behavior Therapies and Medications To Treat Addiction Objectives of Intervention: Rearrange dominance of behavior tracks contingency management (vouchers) motivational enhancement therapeutic communities Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Strengthen prefrontal cortex influence (change thinking process) cognitive and cognitive behavioral tx (unlearn old habits-suppress; learn new skills) assertiveness training (suppress and express) Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alter function of orbitofrontal (saliency) cortex motivational therapy family therapies Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Recovery of function (frontal and obito- frontal cortex) all treatments that keep brain away from drugs for extended time Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated Alleviate underlying psychiatric disorder administer: Antidepressants for depression Ritalin for ADHD Sedatives for anxiety Targets of Medication Methadone, LAAM and Buprenorphine Nicotine gum/patch Naloxone Vmat transporter stimulation DA How some drugs of abuse cause dopamine release: opioids narcotics (activate opioid receptors) nicotine (activate nicotine receptors) vesicle Neuronal terminal Psychostimulants Principles of Behavior Dynamics A B C Prefrontal Cortex C B dopamine initiated GABA and cannabinoid systems critical for function Relieve stress-related drug abuse CRF antagonist Abstinence RELAPSE CRF Anxiety Science is helping to improve our strategies and successes To be successful, treatment is a Lifetime Process Consequence: There is no “cure”…