1. Addiction

2. Copyright © 2006 by Allyn and Bacon Chapter 15 Drug Addiction and the Brain’s Reward Circuits Chemicals That Harm with Pleasure This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program.

3. Copyright © 2006 by Allyn and Bacon Basic Principles of Drug Action Psychoactive drugs – drugs that influence subjective experience and behavior by acting on the nervous system Drug administration – route of administration influences the rate at which and the degree to which the drug reaches its site of action

4. Copyright © 2006 by Allyn and Bacon Drug Administration Ingestion – oral route –Easy and relatively safe –Absorption via digestive tract is unpredictable Injection – bypasses digestive tract –Subcutaneously (SC) – under the skin –Intramuscularly (IM) – into large muscles –Intravenously – into veins – drug delivered directly to brain

5. Copyright © 2006 by Allyn and Bacon Drug Administration Ingestion Injection – SC, IM, IV Inhalation – tobacco and marijuana –Absorbed through capillaries in lungs Absorption through mucous membranes –Nose, mouth, rectum

6. Copyright © 2006 by Allyn and Bacon Mechanisms of Drug Action In order for a psychoactive drug to have an effect, it must get to the brain – it must pass through the blood-brain barrier Action of most drugs terminated by enzymes in the liver – drug metabolism Small amounts may also be excreted in urine, sweat, feces, breath, and mother’s milk

7. Copyright © 2006 by Allyn and Bacon Drug Tolerance Decreased sensitivity to a drug as a consequence of exposure to it – Shift in the dose-response curve Cross tolerance – exposure to one drug can produce tolerance to similar drugs Tolerance often develops to some effects and not others More than one form of tolerance

9. Copyright © 2006 by Allyn and Bacon Drug Tolerance Metabolic –Less drug is getting to the site of action Functional –Decreased responsiveness at the site of action - fewer receptors, decreased efficiency of binding at receptors, receptors less responsive

10. Copyright © 2006 by Allyn and Bacon Physical Dependence Indicated by occurrence of withdrawal –Seen when drug use is terminated –Symptoms are the opposite of the drug’s effects –Body has made changes to compensate for drug’s presence – functions normally with the drug present –Severity varies with drug and pattern of use

12. Copyright © 2006 by Allyn and Bacon Addiction: What Is It? “Addicts” are those who continue to use a drug despite its adverse consequences Addiction and physical dependence are not the same thing While they may co-occur, each can exist independently

13. Copyright © 2006 by Allyn and Bacon Learning in Tolerance and Withdrawal Contingent drug tolerance –Tolerance only develops to drug effects that are experienced Conditioned drug tolerance –Maximal tolerance effects are seen in the environment in which a drug is usually taken Conditioned withdrawal effects –Withdrawal elicited by drug-related cues

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15. Conditioned Tolerance and Withdrawal Situational specificity of drug tolerance is well- documented Environmental cues associated with drug-taking become conditioned stimuli that elicit conditioned compensatory responses, producing tolerance prior to drug use or withdrawal in the absence of the drug

16. Copyright © 2006 by Allyn and Bacon 5 Commonly Abused Drugs Tobacco Alcohol Marijuana Cocaine Opiates

17. Copyright © 2006 by Allyn and Bacon Tobacco Nicotine – major psychoactive ingredient About 70% of those who experiment with smoking become addicted Only about 20% of attempts to stop are successful

18. Copyright © 2006 by Allyn and Bacon Alcohol A depressant High heritability estimate for alcohol addiction - ~55% Metabolic and functional tolerance develops Attacks almost every tissue in the body

19. Copyright © 2006 by Allyn and Bacon Effects of Chronic Alcohol Consumption Severe withdrawal – 3 phases –5-6 hrs post-drinking: tremors, nausea, sweating, vomiting, etc. –15-30 hrs: convulsive activity –24-48 hrs: delirium tremens – may last 3-4 days Korsakoff’s syndrome Cirrhosis

20. Copyright © 2006 by Allyn and Bacon Alcohol and the Brain Reduces flow of Ca ++ into neurons Interferes with 2 nd messenger systems Disrupts GABAergic and glutaminergic transmission Triggers apoptosis

21. Copyright © 2006 by Allyn and Bacon Marijuana Cannabis sativa – common hemp plant THC – primary psychoactive constituent – although over 80 others are present High doses impair short-term memory and interfere with tasks involving multiple steps Addiction potential is low Negative effects are far less severe than those associated with alcohol and tobacco

22. Copyright © 2006 by Allyn and Bacon Adverse Effects of Heavy Marijuana Use Respiratory problems – cough, bronchitis, asthma Single large doses can trigger heart attacks in susceptible individuals No evidence that marijuana causes permanent brain damage

23. Copyright © 2006 by Allyn and Bacon Medicinal Uses of Marijuana Treat nausea Block seizures Dilate bronchioles of asthmatics Decrease severity of glaucoma Reduce some forms of pain

24. Copyright © 2006 by Allyn and Bacon THC Fat-soluble Binds to receptors in basal ganglia, hippocampus, cerebellum, and neocortex Endogenous ligand is anandamide Function of anandamide is not known

25. Copyright © 2006 by Allyn and Bacon Stimulants Increase neural and behavioral activity Cocaine and its derivatives – commonly abused Crack – a potent, cheap, and smokable form of cocaine Cocaine is an effective local anesthetic –Synthetic analogues procaine and lidocaine used today

26. Copyright © 2006 by Allyn and Bacon Cocaine Cocaine binges or sprees may lead to cocaine psychosis –Looks like paranoid schizophrenia While tolerance may develop to some effects of cocaine, sensitization is seen to motor and convulsive effects Although highly addictive, withdrawal is relatively minor

27. Copyright © 2006 by Allyn and Bacon Amphetamine AKA “speed” – another abused stimulant Effects are comparable to those of cocaine – also can produce psychosis MDMA (ecstasy) – a relative of amphetamine Evidence suggests that stimulants are neurotoxins

28. Copyright © 2006 by Allyn and Bacon Ecstasy Studies of lab animals find that MDMA has toxic effects on serotonergic and dopaminergic neurons But are the doses used in studies comparable to what humans use? Human studies do find abnormalities of serotonergic function and deficits in memory, mood, and psychomotor tasks

29. Copyright © 2006 by Allyn and Bacon Opiates: Heroin and Morphine Morphine and codeine obtained from the opium poppy Opiates – these drugs and others with similar structures or effects Medicinal uses –Analgesics (painkillers) –Treatment of cough and diarrhea High risk of addiction

30. Copyright © 2006 by Allyn and Bacon Factors Increasing Opiate Popularity China’s ban of tobacco smoking led to opium smoking –More addicting than eating opium Isolation of morphine –Opium’s most potent constituent The hypodermic needle –During the Civil War morphine addiction came to be known as “soldiers’ disease”

31. Copyright © 2006 by Allyn and Bacon U.S. Opiate History Readily available in a variety of “potions” until 1914 Harrison Narcotic Act (1914) –Illegal to sell or use opium –Heroin, a synthetic opiate, was still legal Structure similar to morphine, but better able to cross the blood-brain barrier More addictive Heroin illegal as of 1924

32. Copyright © 2006 by Allyn and Bacon Opiate Addiction Drawn to use by the rush following IV injection Tolerance and physical dependence develop Desire to avoid withdrawal adds to motivation to use Although highly addictive, direct health hazards are relatively minor Many health hazards related to use of needles Severity of withdrawal has been exaggerated

33. Copyright © 2006 by Allyn and Bacon Treatment for Heroin Addiction Opiates bind to endorphin receptors Methadone binds to these receptors –Produces less pleasure –Administered orally –Prevents withdrawal Buprenorphine – similar to methadone but longer lasting Substituting a less dangerous drug for the abused drug

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35. Reducing Drug Abuse Current approaches are not effective. What recommendations would you make to decrease the incidence of drug abuse? Which abused drugs should we be most concerned about?

36. Copyright © 2006 by Allyn and Bacon Biopsychological Theories of Addiction Physical-Dependence Theory – –Use continues to avoid withdrawal Why relapse after detoxification? Why begin use? Why does addiction develop to drugs that do not produce severe withdrawal? Positive-Incentive Theories –Use continues due to craving for drug effects –Supported by research

37. Copyright © 2006 by Allyn and Bacon Causes of Relapse Stress –Drug use as a coping mechanism Priming –A single exposure leads to a relapse Environmental cues

38. Copyright © 2006 by Allyn and Bacon Pleasure Centers of the Brain Brain circuitry exists that makes certain behaviors pleasurable Many species will work for stimulation of brain “pleasure centers” Discovered by Olds and Milner Drug use may be reinforced by acting on this circuitry

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40. Mesotelencephalic Dopamine (DA) System and Self-Stimulation DA neurons projecting from the midbrain to areas in telencephalon Nigrostriatal pathway –Substantia nigra > Dorsal striatum Mesocorticolimbic pathway –Ventral tegmental area > cortical and limbic sites –Involved in reward

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42. Mesocorticolimbic Pathway and Reward Self-stimulation sites that do not contain DA neurons project here Increase in DA release seen here in self- stimulation studies DA agonists tend to increase self-stimulation and antagonists to decrease Lesions here disrupt self-stimulation

43. Copyright © 2006 by Allyn and Bacon Neural Mechanisms of Motivation and Addiction How do drugs act on existing reward circuitry to motivate addicts to continue to use? Asking animals what they like – necessary to explore positive-incentive theories –Drug self-administration –Conditioned place-preference

44. Copyright © 2006 by Allyn and Bacon Behavioral preference tests

45. Copyright © 2006 by Allyn and Bacon Dopamine and Drug Addiction DA’s role suggested by self-stimulation studies DA antagonists interfere with self- stimulation and reduce the reinforcing effects of food Nucleus accumbens appears to play a primary role

46. Copyright © 2006 by Allyn and Bacon Nucleus Accumbens (NA) and Drug Addiction Animals self-administer microinjections of addictive drugs into NA Microinjection of drugs into NA produce conditioned placed preferences Lesion NA or ventral tegmental area – no drug self- administration or drug-related place preference Both self-administration of addictive drugs and natural reinforcers result in increased dopamine in the NA

47. Copyright © 2006 by Allyn and Bacon DA and Addiction Role is well-established Cocaine acts as a DA agonist by binding to DA transporters and blocking reuptake Addicts only report a high when cocaine is effectively blocking DA reuptake, increasing extracellular dopamine IV amphetamine study – euphoria reported correlated with DA levels in nucleus accumbens

48. Copyright © 2006 by Allyn and Bacon Addiction While pieces of the puzzle are understood, many questions remain Some studies suggest that DA is involved in expecting reward, as opposed to reward itself Considering what we do know, how can addiction best be explained?