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NIDA NATIONAL INSTITUTE ON DRUG ABUSE Bringing the Full Power of Science to Bear on Drug Abuse & Addiction Neurotoxicity AIDS, Cancer NEUROTOXICITY AIDSMental illness CANCER MENTAL ILLNESS Homelessness Crime Violence Health care Productivity Accidents 4 Out of 10 U.S. AIDS Deaths Are Related to Drug Abuse Estimated Economic Cost to Society from Substance Abuse and Addiction: Illegal drugs: $181 billion/year Alcohol: $185 billion/year Tobacco: $158 billion/year Total: $524 billion/year Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000. What is Addiction? Addiction is A Brain Disease • Characterized by compulsive behavior • The continued abuse of drugs despite negative consequences • A chronic, potentially relapsing disorder Advances in science have revolutionized our fundamental views of drug abuse and addiction. used to be Your Brain on Drugs Today Front of Brain Back of Brain 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 Fowler et al., Synapse, 1989. YELLOW shows places in brain where cocaine binds (striatum) Addiction is Like Other Diseases… It is preventable. It is treatable It changes biology. If untreated, it can last a lifetime. Decreased Brain Metabolism in Drug Abuser Healthy Brain Diseased Brain/ Cocaine Abuser High Low Decreased Heart Metabolism in Heart Disease Patient Healthy Heart Diseased Heart Research supported by NIDA addresses all of these components of addiction Addiction Involves Multiple Factors Addiction Is A Developmental Disease that starts in adolescence and childhood % in each age group who develop dependence first-time first 1.8% 1.8% TOBACCO CANNABIS ALCOHOL 1.6% 1.6% 1.4% 1.4% 1.2% 1.2% 1.0% 1.0% 0.8% 0.8% 0.6% 0.6% 0.4% 0.4% 0.2% 0.2% 0.0% 0.0% 55 10 10 15 15 21 21 25 25 30 30 35 35 40 40 45 45 50 50 55 55 60 60 65 65 Age Age at tobacco, alcohol and cannabis dependence per DSM IV National National Epidemiologic Epidemiologic Survey Survey on on Alcohol Alcohol and and Related Related Conditions Conditions ,, 2003. 2003. Why Do People Take Drugs in The First Place? To feel good To have novel: feelings sensations experiences AND to share them To feel better To lessen: anxiety worries fears depression hopelessness Why Do People Abuse Drugs? Drugs of Abuse Engage Systems in the Motivation and Pleasure Pathways of the Brain movement motivation Dopamine addiction Reward & well-being Drugs are “Imposters” of Brain Messages The Neuron: How the Brain’s Messaging System Works Dendrites Axon Cell body (the cell’s life support center) Terminal branches of axon Neuronal Impulse Myelin sheath Donald Bliss, MAPB, Medical Illustration dopamine transporters Natural Rewards Elevate Dopamine Levels SEX 200 % of Basal DA Output NAc shell 150 100 Empty 50 Box Feeding 200 150 100 15 10 5 0 0 0 60 120 Time (min) Di Chiara et al., Neuroscience, 1999. 180 Copulation Frequency DA Concentration (% Baseline) FOOD Female Present Sample Number 1 2 3 4 5 6 7 8 Fiorino and Phillips, J. Neuroscience, 1997. Mounts Intromissions Ejaculations Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 AMPHETAMINE DA DOPAC HVA 250 1 2 3 4 Time After Amphetamine % of Basal Release 400 0 Accumbens Caudate 150 100 0 0 1 2 3 hr Time After Nicotine COCAINE DA DOPAC HVA 200 100 0 5 hr 0 NICOTINE 200 Accumbens 300 250 % of Basal Release % of Basal Release % of Basal Release Effects of Drugs on Dopamine Release 1 2 3 4 Time After Cocaine Accumbens 5 hr MORPHINE Dose (mg/kg) 0.5 1.0 2.5 10 200 150 100 0 0 1 2 3 4 Time After Morphine 5hr Di Chiara and Imperato, PNAS, 1988 But Dopamine is only Part of the Story Other neurotransmitter systems are also affected: • Serotonin: mood regulation, sleep • Glutamate: learning and memory Science Has Generated Much Evidence Showing That… Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways AND… We Have Evidence That These Changes Can Be Both Structural and Functional Structurally… NA C Saline Amph Source: Robinson & Kolb, Journal of Neuroscience, Volume: 1997 Functionally… Dopamine D2 Receptors are Lower in Addiction DADA Cocaine DA DA DA DA DA DA DA DADA DA Meth Reward Circuits Non-Drug Abuser DADA Alcohol DA DA DA DA Heroin Reward Circuits Control Addicted Drug Abuser Normal Control Dopamine Transporter Bmax/Kd Dopamine Transporters in Methamphetamine Abusers 2.0 1.8 1.6 1.4 1.2 1.07 Motor Task Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. 8 9 10 11 12 13 Time Gait (seconds) 2.0 1.8 1.6 1.4 1.2 1.0 16 14 12 10 8 Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment. 6 Delayed Recall (words remembered) Methamphetamine Abuser 4 Volkow et al., Am. J. Psychiatry, 2001. Implication: Brain changes resulting from prolonged use of drugs may compromise mental and motor functions Circuits Involved In Drug Abuse and Addiction All of these must be considered in developing strategies to effectively treat addiction