2. PSYC 2920 Lecture 7

3. Dependence, Addiction and the Self-Administration of Drugs History of Addiction Research Addiction as a Disease Addiction as a Disease DSM IV disease = disorder disease = disorder Gives substance abuse the status of “diseases” Gives substance abuse the status of “diseases” What are the practical consequences of labeling something as a disease? Funding Funding Public perception Public perception

4. Dependence, Addiction and the Self-Administration of Drugs History of Addiction Research Predisposition Predisposition Either born or predisposed to drug abuse E.M. Jellinek E.M. Jellinek The Disease Concept of Alcoholism The Disease Concept of Alcoholism Alcoholics Anonymous Alcoholics Anonymous Drug Exposure Drug Exposure Addition is caused by exposure Is Addiction a Disease Is Addiction a Disease

5. Addiction DSM-IV Substance Dependence: A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three or more of the following within the same 12-month period… Substance Dependence: A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three or more of the following within the same 12-month period…

6. DSM-IV Criteria for Substance Dependence ToleranceWithdrawal Substance taken in larger amounts or over longer period than intended Persistent desire or unsuccessful efforts cut down or control use Great deal of time is spent in activities necessary to obtain the substance or recover from its effects Important social, occupational, or recreational activities are given up or reduced because of use The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance

7. DSM-IV Criteria for Substance Abuse A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period: Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions or expulsions from school; neglect of children or household) Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions or expulsions from school; neglect of children or household) Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use) Recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use) Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct) Recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct) Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights) Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights) B. The symptoms have never met the criteria for Substance Dependence for this class of substance.

8. Dependence, Addiction and the Self-Administration of Drugs Addiction as Physical Dependence Background Background Withdrawal or Abstinence Syndrome Physical or Physiological Dependence DependenceTolerance Habituation Habituation Condition in which the user desires a drug, but suffers not ill effects on its discontinuance The term “habituation” is no longer commonly used in this way. The term “habituation” is no longer commonly used in this way. Psychological Dependence Psychological Dependence Circular Definition

9. Dependence, Addiction and the Self-Administration of Drugs Addiction as Physical Dependence Problems with the Physical and Psychological Dependence Theories Problems with the Physical and Psychological Dependence Theories Not all develop physical dependence Some will voluntarily stop taking a drug even with the presence of withdrawal symptoms Psychological dependence is circular in reasoning

10. Dependence, Addiction and the Self-Administration of Drugs Modern Behavioral and Neuroscientific Explanations Background Background Flavor toxicosis learning Animals won’t do drugs if they taste bad Animals won’t do drugs if they taste bad Only human can become addicted (disproven) Only human can become addicted (disproven) Positive reinforcement model Positive reinforcer is any stimulus that increases the frequency of a behavior it is contingent on. Positive reinforcer is any stimulus that increases the frequency of a behavior it is contingent on.

11. Dependence, Addiction and the Self-Administration of Drugs Drug Self-Administration in Animals

12. Dependence, Addiction and the Self-Administration of Drugs Drugs as Positive and Negative Reinforcers Self-Administration via Other Routes Self-Administration via Other RoutesIntragastricIntracranialIntraventricularInhalation Drugs as Aversive Stimuli Drugs as Aversive Stimuli Not all drugs have positive reinforcers LSD in animals

13. Dependence, Addiction and the Self-Administration of Drugs Self-Administration The similarity between the patterns of self- administration of ethanol in a human and a rhesus monkey under continuous drug availability. The arrows indicate the occurrence of withdrawal symptoms.The similarity between the patterns of self- administration of ethanol in a human and a rhesus monkey under continuous drug availability. The arrows indicate the occurrence of withdrawal symptoms.

14. Dependence, Addiction and the Self-Administration of Drugs Drugs as Positive and Negative Reinforcers Problems with the Positive Reinforcement Model Problems with the Positive Reinforcement Model Discounting delay Circularity

15. Dependence, Addiction and the Self-Administration of Drugs Self-Administration in Humans and Nonhumans Mello & Mendelson (1987) Mello & Mendelson (1987)Ethical? Similarities and Differences Between Human and Nonhuman Animals Similarities and Differences Between Human and Nonhuman Animals Not a great deal of difference between species Type of drug Patterns of Self-Administration Patterns of Self-Administration

16. Why use animal models? Experimental control Can separate variables from each other more easily Can separate variables from each other more easily Reward and stress brain systems are common to many vertebrates, particularly mammals Major differences between humans and other mammals is with cortical and neocortical structures Major differences between humans and other mammals is with cortical and neocortical structures More direct probing of structural and pharmacological contributions to drug-related behaviour can be conducted lesions lesions drug administration drug administration recording recording

17. Modeling addiction in non-human species Must distinguish casual drug use from drug dependence Successful models of dependence should mimic the DSM-IV criteria for drug dependence Compulsion to seek and take the drug Compulsion to seek and take the drug Loss of control in limiting intake Loss of control in limiting intake Emergence of negative emotional state (e.g., dysphoria, anxiety, tability) when access to the drug is prevented Emergence of negative emotional state (e.g., dysphoria, anxiety, tability) when access to the drug is prevented

18. Dependence, Addiction and the Self-Administration of Drugs Measuring the Reinforcing Value of Drugs Rate of Responding Rate of Responding Progressive Ratio Progressive Ratio Breaking point Organism will stop responding Organism will stop responding Choice Choice Two levers; one has consequences Place Conditioning Place Conditioning Animal will spend time in area of reinforcement

19. Conditioned place preference A model of drug-seeking behaviour Relies on classical rather than operant conditioning Drug administration does not require a response from the animal Drug administration does not require a response from the animal Procedure (unbiased version) Preconditioning: days 1-3 Preconditioning: days 1-3 Conditioning: days 4-7 Conditioning: days 4-7 Test: day 5 Test: day 5 State-dependent learning test: day 6 (often not done) State-dependent learning test: day 6 (often not done) Strength of association depends on drug dose and number of conditioning sessions

20. Conditioned place preference

21. Dependence, Addiction and the Self-Administration of Drugs Factors That Alter the Reinforcing Value of Drugs Reinforcing Value of Different Drugs Reinforcing Value of Different Drugs Abuse potential Abuse liability Dose of Drug Dose of Drug Genetic Differences Genetic Differences Relief of Unpleasant Symptoms Relief of Unpleasant Symptoms Task Demands Task Demands Stress Stress

22. Social stress findings: Amphetamine Social stress: starting on day 30, daily 1-hr isolation in a round, ventilated plastic container (approx. 10 cm diameter and 10 cm high) After isolation, rats were returned to the colony and housed each day with a new cage partner that was also undergoing the stress procedure. on Day 45, rats were housed with their original cage partner. maintenance.

23. CPP stress findings Fewer conditioning sessions required for cocaine-seeking behaviour in conditioned place preference model in rats that are reared alone vs. in groups alone vs. in groups in impoverished environments vs. with toys in impoverished environments vs. with toys Rightward shift in amphetamine dose response (indicative of tolerance) in rats where dams have been exposed to stress

24. Genetics Strains of rats bred to mimic human alcohol- dependent individuals Marchigian Sardinian alcohol-preferring (msP) rats Some evidence that genetic differences in humans contribute to alcohol dependence Related to breakdown of metabolic products of alcohol May be rooted in historical calorie hoarding (i.e. agrarian vs. hunter gatherer societies