Common Features of Addiction Physical versus Psychological Addiction Tolerance:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Common Features of Addiction • Craving and Relapse • Reinstatement model: • An animal is trained to make a response that is reinforced by in intravenous injection of a drug. • Next, the response is extinguished by providing injections of a saline solution. • Once responding has extinguished, the animal is given a free injection of the drug. • In response to the drug, the animal begins responding once again.

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. Common Features of Addiction • Craving and Relapse • Brain mechanisms: • PET scan studies have demonstrated activity of the prefrontal cortex and the anterior cingulate cortex of cocaine abusers was less active than that of normal subjects during abstinence.

9. 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.

10. Common Features of Addiction • Craving and Relapse • Stress: • Stress is associated with the release of CRH in the brain by cells of the central nucleus of the amygdala whose terminals release this peptide in the bed nucleus of the stria terminalis.

11. Commonly Abused Drugs • Opiates • Cocaine and Amphetamines • Nicotine • Alcohol and Barbiturates • Cannabis

12. Common Features of Addiction • Opiates: • Endogenous opiates are secreted when an animal is performing behaviors that are important to its survival such as fighting with another animal.

13. Common Features of Addiction • Opiates: • Endogenously released opioids stimulate receptors that produce analgesia that reduces the inhibitory effects of pain and positive reinforcement that encourages the animal to continue with what is was doing.

14. 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.

15. 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

16. Common Features of Addiction • Neural Basis of Reinforcing Effects • Dynorphin: • An endogenous opioid; the natural ligand for k-opiate receptors. • Conditioned place preference: • The learned preference for a location in which an organism encountered a reinforcing stimulus, such as food or a reinforcing drug.

17. Common Features of Addiction • Neural Basis of Reinforcing Effects • Naloxone: • A drug that blocks mu opiate receptors; antagonizes the reinforcing and sedative effects of opiates. • Pimozide: • A drug that blocks dopamine receptors.

18. Common Features of Addiction • Neural Basis of Withdrawal Effects • Brain mechanisms: • Several regions of the brain have been implicated in withdrawal effects including the periaqueductal gray matter, the locus coeruleus, and the amygdala.

19. 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.

20. 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.

21. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

30. 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.

31. 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.

32. 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.

34. 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.

35. Common Features of Addiction • Alcohol and Barbiturates • Sites of action: • Alcohol has two primary sites of actions. It serves as an indirect agonist at GABAA receptors and as an indirect antagonist at NMDA receptors. • Stimulation of both receptors systems triggers apoptosis (cellular death).

36. 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.

37. 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.

38. 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.

39. Common Features of Addiction • Alcohol and Barbiturates • Brain mechanisms: • Alcohol enhances the action of GABA and GABAA 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.

40. 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 GABAA receptor.

41. 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.

42. 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.

43. 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.

45. 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.