1. Copyright (c) Allyn & Bacon 2004 1 Chapter 16 Drug Abuse 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.

2. Copyright (c) Allyn & Bacon 2004 2  Common Features of Addiction  Physical versus Psychological Addiction  Tolerance: The fact that increasingly large doses of drugs must be taken to achieve a particular effect; caused by compensatory mechanisms that oppose the effect of the drug.

3. Copyright (c) Allyn & Bacon 2004 3  Common Features of Addiction  Physical versus Psychological Addiction  Withdrawal symptoms: The appearance of symptoms opposite to those produced by a drug when the drug is suddenly no longer taken; caused by the presence of compensatory mechanisms.

4. Copyright (c) Allyn & Bacon 2004 4  Common Features of Addiction  Positive Reinforcement  Positive reinforcement: Addictive drugs have reinforcing effects. That is, their effects include activation of the reinforcement mechanism. This activation strengthens the response that was just made, namely, taking the drug. Drugs with the most immediate effects tend to be the most addictive.

5. Copyright (c) Allyn & Bacon 2004 5  Common Features of Addiction  Negative reinforcement  Negative reinforcement: The removal or reduction of an aversive stimulus that is contingent on a particular response, with an attendant increase in the frequency of that response. If taking a drug “turns off” aversive withdrawal effects it is a negatively reinforced behavior that will increase in frequency.

6. Copyright (c) Allyn & Bacon 2004 6  Common Features of Addiction  Craving and Relapse  Craving: The desire to take a drug.  Relapse: A return to the use of a drug following a period of abstinence from use of the drug.

7. Copyright (c) Allyn & Bacon 2004 7  Common Features of Addiction  Craving and Relapse  Brain mechanisms: Relapse appears to involve activation of the mesolimbic system of dopaminergic neurons. Relapse caused by stimuli previously associated with cocaine appears to involve the amygdala as well as the mesolimbic dopamine system

8. Copyright (c) Allyn & Bacon 2004 8  Common Features of Addiction  Craving and Relapse  Stress: Clinicians have long observed that stressful situations can cause a former drug addict to relapse. Stressful stimuli, even those that occur early in life, increase an animal’s susceptibility to drug addiction.

9. Copyright (c) Allyn & Bacon 2004 9  Commonly Abused Drugs  Opiates  Cocaine and Amphetamines  Nicotine  Alcohol and Barbiturates  Cannabis

10. Copyright (c) Allyn & Bacon 2004 10  Common Features of Addiction  Opiates: Opium is derived from a sticky resin produced by the opium poppy and has been eaten or smoked for centuries. Heroin is the most commonly abused opiate.

11. Copyright (c) Allyn & Bacon 2004 11  Common Features of Addiction  Neural Basis of Reinforcing Effects  Opiate Administration: When an opiate is administered it stimulates opiate receptors located on neurons in various parts of the brain and cause a variety of effects including: Analgesia Hypothermia Sedation Reinforcement

12. Copyright (c) Allyn & Bacon 2004 12  Common Features of Addiction  Neural Basis of Reinforcing Effects  Periaqueductal gray matter (PAG): Stimulation of the PAG opiate receptors cause analgesia.  Preoptic area: Stimulation of the preoptic area opiate receptors cause hypothermia (reduction of body temperature).

13. Copyright (c) Allyn & Bacon 2004 13  Common Features of Addiction  Neural Basis of Reinforcing Effects  Mesencephalic reticular formation: Stimulation of the opiate receptors in the mesencephalic reticular formation cause sedation.  Ventral Tegmental area (VTA) and the nucleus accumbens: Stimulation of the opiate receptors in the VTA and nucleus accumbens play a role in the reinforcing effects of opiates.

14. Copyright (c) Allyn & Bacon 2004 14  Common Features of Addiction  Cocaine and Amphetamine Cocaine and amphetamine have similar behavioral effects, because both act as potent dopamine agonists. The site of action of cocaine and amphetamine are different.

15. Copyright (c) Allyn & Bacon 2004 15  Common Features of Addiction  Cocaine and Amphetamine  Cocaine: Cocaine binds with and deactivates the dopamine transporter proteins, thus blocking the reuptake of dopamine after it is released by terminal buttons, thus acting as a dopamine agonist.

16. Copyright (c) Allyn & Bacon 2004 16  Common Features of Addiction  Cannabis  Brain mechanisms: THC administration stimulates release of dopamine in the nucleus accumbens and the ventral tegmental area The drug appears to act directly on dopaminergic terminal buttons-presumably on presynaptic heteroreceptors.

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19. Copyright (c) Allyn & Bacon 2004 19  Common Features of Addiction  Cocaine and Amphetamine  Amphetamine: Amphetamine inhibits the reuptake of dopamine, but its most important effects is to directly stimulate the release of dopamine from terminal buttons.

20. Copyright (c) Allyn & Bacon 2004 20  Common Features of Addiction  Cocaine and Amphetamine  Effect of cocaine and amphetamine: The effects of cocaine and amphetamine seen in people who abuse these drugs regularly include psychotic behavior: hallucinations, delusions of persecution (paranoid behavior), mood disturbances, and repetitive motor behaviors.

21. Copyright (c) Allyn & Bacon 2004 21  Common Features of Addiction  Cocaine and Amphetamine  Effect of cocaine and amphetamine: Prior abusers of methamphetamine showed a decrease in the number of dopamine transporters in the caudate nucleus and putamen, despite a three year abstinence from the drug.

22. Copyright (c) Allyn & Bacon 2004 22  Common Features of Addiction  Cocaine and Amphetamine  Effect of cocaine and amphetamine: Both drugs are potent dopamine agonists, these drugs activate the mesolimbic system and reinforce drug-taking behavior. Both drugs increase the concentration of dopamine in the nucleus accumbens that is a critical site in the reinforcing effect of the drugs.

23. Copyright (c) Allyn & Bacon 2004 23  Common Features of Addiction  Cocaine and Amphetamine  Effect of cocaine and amphetamine: Long-term cocaine or amphetamine use does not produce tolerance and is even likely to produce sensitization to the effects of the drug. Withdrawal from cocaine does not cause physical symptoms, but it does cause unpleasant feelings, including dysphoria and decreased ability to feel pleasure.

24. Copyright (c) Allyn & Bacon 2004 24  Common Features of Addiction  Nicotine  Nicotine: Nicotine is an addictive drug and it accounts for more deaths than the so-called “hard drugs”. The World Health Organization reported that one-third of the adult population of the world smokes. Investigators estimate that by the year 2020, tobacco will be the largest single health problem worldwide, with 8.4 million deaths per year.

25. Copyright (c) Allyn & Bacon 2004 25  Common Features of Addiction  Nicotine  Nicotine: Forty percent of people continue to smoke after having had a laryngectomy (which is usually performed to treat throat cancer). More than 50 percent of heart attack survivors continue to smoke, and about 50 percent of people continue to smoke after submitting to surgery for lung cancer.

26. Copyright (c) Allyn & Bacon 2004 26  Common Features of Addiction  Nicotine  Nicotine: Nicotine stimulates acetylcholine receptors and increases the activity of dopaminergic neurons of the mesolimbic system, which contain these receptors, and caused dopamine to be released in the nucleus accumbens. Injections of a nicotine agonist into the ventral tegmental area will reinforce a conditioned place preference.

27. Copyright (c) Allyn & Bacon 2004 27  Common Features of Addiction  Alcohol and Barbiturates  Alcohol: Alcohol has greater costs to society than any other drug. A large percentage of deaths and injuries caused by motor vehicle accidents are related to alcohol. The leading cause of mental retardation in the Western world today is alcohol consumption by pregnant women.

28. Copyright (c) Allyn & Bacon 2004 28  Common Features of Addiction  Alcohol and Barbiturates  Sites of action: Alcohol has two primary sites of actions. It serves as an indirect agonist at GABA A receptors and as an indirect antagonist at NMDA receptors. Stimulation of both receptors systems triggers apoptosis (cellular death).

29. Copyright (c) Allyn & Bacon 2004 29  Common Features of Addiction  Alcohol and Barbiturates  Behavioral effects: At low doses alcohol produces mild euphoria and has an anxiolytic effect (reduces anxiety). At higher doses alcohol produces uncoordination and sedation.

30. Copyright (c) Allyn & Bacon 2004 30  Common Features of Addiction  Alcohol and Barbiturates  Behavioral effects: The mild euphoria of alcohol provides positive reinforcement for continued drinking. Alcohol also relieves anxiety and continued use is negatively reinforced.

31. Copyright (c) Allyn & Bacon 2004 31  Common Features of Addiction  Alcohol and Barbiturates  Brain mechanisms: Alcohol, like other addictive drugs, increases the activity of the dopaminergic neurons of the mesolimbic system and increases the release of dopamine in the nucleus accumbens.

32. Copyright (c) Allyn & Bacon 2004 32  Common Features of Addiction  Alcohol and Barbiturates  Brain mechanisms: Alcohol enhances the action of GABA and GABA A receptors and interferes with the transmission of glutamate at NMDA receptors. The perceptual effects of alcohol are mimicked by both GABA agonists and NMDA antagonists.

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34. Copyright (c) Allyn & Bacon 2004 34  Common Features of Addiction  Alcohol and Barbiturates  Brain mechanisms: Observations strongly suggest that NMDA receptors are responsible for the seizures produced by alcohol withdrawal. The sedative effect of alcohol also appears to exerted at the GABA A receptor.

35. Copyright (c) Allyn & Bacon 2004 35  Common Features of Addiction  Cannabis  Cannabis: THC is the active ingredient in marijuana. The site of action is the endogenous cannabinoid receptor in the brain, the CB1 receptor, has been discovered, and the distribution of this receptor has been mapped.

36. Copyright (c) Allyn & Bacon 2004 36  Common Features of Addiction  Cannabis  Brain mechanisms: The hippocampus contains a large concentration of THC receptors. Marijuana is known to affect people’s memory by disrupting the normal functioning of the hippocampus.

37. Copyright (c) Allyn & Bacon 2004 37  Common Features of Addiction  Cannabis  Long-term damage: The effects of long-term marijuana use include bronchitis, increased risk of lung cancer, poor ability to control the use of the drug, minor impairments of attention and memory, and slower choices in decision making tasks. Cognitive impairments from long-term use appear to be subtle.

38. Copyright (c) Allyn & Bacon 2004 38  Heredity and Drug Abuse  Heritability Studies of Humans In general, studies have found that the heritability of smoking is just as strong as that of alcoholism. A twin study found that alcoholism and nicotine dependence have genetic factors in common, which explains why alcoholics are often addicted to nicotine.