Dependence, Addiction, and the Self-Administration of Drugs Ryan Webber

Explaining Drug Self-Administration Try to use scientific theory to explain testable and reproducible theories on why drugs are abused Three Models: 1.Disease model 2.Dependence model 3.Positive reinforcement model (learning)

Explaining Drug Self-Administration Models not the same as theories, models are not mutually exclusive; if one is correct, the others are not necessarily wrong All try to explain Why behavior of drug addicts appears to be different from normal behavior Why there are considerable differences between individuals in the development of drug abuse

Disease Model Addictive behavior not the same as normal behavior because it is compulsive (beyond an individual’s control) and can be sometimes self-destructive Disease model suggest that these “abnormal” behaviors are caused by a disease state brought on by drug usage

Disease Model History In mid-19th century, drug abusers were considered deficient in character, moral fiber, willpower, and/or self- control – sinners and criminals For this reason, only priests and clerics treated abuse American social reform movements in the late 1800’s changed drug abuse viewpoints American Association for the Cure of Inebriates – “Inebriety is a disease” Physicians widely prescribed laudanum (opium and alcohol) – felt that they should help stop abuse of the drug

Disease Model History Model faded until 20th century when Alcoholics Anonymous became popular – core tenet is that “alcoholism is a disease and that alcoholics cannot control their drinking and cannot be held responsible for their excessive intake and its effects” DSM-IV does not use the term disease, but is a disorder – classifies it as a clinically significant psychological syndrome or pattern that is associated with present distress or disability

Strengths / Problems of the Disease model Explains why behaviors are not normal within addicts – they are suffering from disease Also explains why only some people become addicts – diseases only strike some individuals No “diseases” have ever been identified, what kind they are, and how these diseases can make people take drugs

The Physical Dependence Model Uses the phenomenon of withdrawal to explain why people are addicted to drugs Sickness caused after drug cessation originally explained by autotoxin, a metabolite of the drug taken – really caused by physical dependence Withdrawal sickness is exceptionally unpleasant, fear of withdrawal can explain the lengths drug abusers take to avoid going through it Theory works well for abuse of opiates, alcohol, and barbiturates Does not explain the use of many other drugs such as cocaine and cannabis which do not produce withdrawal sickness

Psychological Dependence Physical dependence doesn’t explain all drug abuse; scientists theorized that something more subtle was occurring Thought to take place in the brain and did not have any other symptoms other than it manifested itself as a craving Circular argument – can’t say that psychological dependence causes drug abuse if you say that drug abuse causes psychological dependence Need more proof, none exists for either physical or psychological dependence

Positive Reinforcement History Until the 1950’s drug abuse was thought as a human disease, animals did not have free will and could not sin by using drugs (addiction was thought of as punishment) Not reproducible because researchers used oral introduction when testing drugs Delay between ingestion and effect of drugs which most likely affected learning Most drugs have a bitter taste that animals dislike and most animals have built-in protection called flavor toxicosis learning which causes taste aversion if ingestion is followed by sickness or altercation in the nervous system

Positive Reinforcement History During 1950’s researchers realized that laboratory animals learned to perform behavior that resulted in a drug injection Drug infusion acted like a traditional positive reinforcer such as food or water (Thompson and Schuster 1964) Positive reinforcer – any stimulus that increases the frequency of a behavior it is contingent on Some drugs cause avoidance response due to their aversive properties – LSD, the antipsychotic drug chlorpromazine, and the antidepressant imipramine

Positive Reinforcement Problems Why can drug abuse be positive enough for some individuals to take the drug, while for others it will be adversive? Why don’t punishing consequences have negative effects which counter the ones caused by drug abuse?

Positive Reinforcement More traditional reinforcers such as food can be destructive and cause pain People overeat and become obese which causes physical discomfort, health risks, and social censure Sexual activity, gambling Alcohol’s pleasure takes place soon after ingestion; hangovers occur hours later, learning has already occurred before someone gets sick

Reinforcement Centers Reinforcement centers discovered in the brain associated with the limbic system that control the motivational behaviors of eating, drinking, and sexual activity

Reinforcement Center Stimuli can act as reinforcers without the sensation of pleasure Pleasure is caused by the activation of the mesolimbic dopamine system The system exists not to make someone feel good, but to make them repeat certain actions

Reinforcing Effects of Drugs Drugs can control behavior by utilizing the same brain mechanism as other reinforcers like food Natural reinforcers have a satiation mechanism that terminates their reinforcing effect Example: Food is only a reinforcer if there is hunger; after a certain amount is eaten food loses its value Most drugs don’t appear to have any natural limits to their reinforcement

Drug use Between Human and Nonhuman Animals Not a great deal of difference between species (Griffiths, Bigelow, and Henningfield 1980) Nonhumans don’t find hallucinogens to be reinforcing, and do not readily self- administer the active ingredient in cannabis, THC

Incentive Ability of drugs to act as reinforcers is not constant Very tasty or nourishing foods can be powerful reinforcers while foods that are not so tasty or nourishing may only be of limited effectiveness Foods may also only be reinforcers if an animal has been deprived of it for awhile

Incentive Value of Different Drugs Drugs, like foods have different capacity to act as reinforcers – this property called abuse potential or abuse liability Some drugs have varying durations of action Other drugs such as Phenobarbital cause animals to go to sleep and cannot dose themselves again

Progressive Ratio, Choice, and Dose Incentive problems can be overcome by using a progressive ratio schedule Animals given a drug only after a certain behavior is exhibited (example: pulling a leaver) Eventually can increase the quantity of behavior needed before reward given Still has problems with drugs that can affect the behavior

Progressive Ratio, Choice, and Dose Give animals two levers, keyed for a drug each Given choice, animal should respond to lever that delivers more reinforcing drug Larger doses generally more reinforcing than smaller doses, but when reach too large can be adversive

Genetic Differences Positive reinforcement model emphasizes environmental and schedule variations are important to drug-self administration, but doesn’t preclude biochemical and genetic factors Certain strains of mice have been bred to be alcohol-preferring or avoiding Men with a family history of alcoholism are at greater risk of becoming alcoholics themselves (Schuckit 1985) Different strains of rats and have been found to have preferences for cocaine and opiates

Relief of Unpleasant Symptoms Use medications to relieve symptoms of stress De Wit and Johnson (1987) diazepam (Valium) and placebo for normal population and then high anxiety population – no self-administration Pirec et al 1995 – opiates will be self- administered if participants know they will experience pain

Task Demands Use of drug depends on demands of expected situation Silverman 1995 – color-coded capsules of a tranquilizer or stimulant Participants either required to perform vigilance task or relaxation task Seven of eight chose amphetamine with vigilance task, all eight with relaxation task

Stress Stress like hunger can increase incentive value Stress in animals can be caused by tail pinch, social isolation, exposure to aggression, and unpredictable foot shock Stress hormones cause the release of dopamine in the nucleus accumbens and can act as reinforcers Dopamine system stimulation intensifies incentive value of drug and related stimuli

Stress (continued) Studies of US service personel in Vietnam showed many were using high-grade heroin on a regular basis, when returned to the US, many stopped

Previous Experience with Other Drugs – Gateway Drugs Bergman and Johanson (1985) baboons do not self-administer diazepam when switched to it from cocaine THC Did when switched from pentobarbital

Physical dependence Not necessary for drug-taking self administration, but withdrawal can influence the strength of the reinforcement Tomoji Yangita (1987) compared breaking points between animals pretreated with a drug or placebo

Priming Response to a reinforcer can be stimulated by noncontingent presentation of that reinforcer J. Stewart and de Wit (1987) trained monkeys to press a bar for heroin or cocaine, stopped treatments After one infusion, animals would start pressing the bar again Priming explains loss of control in alcoholics Exposure to a formerly abused drug causes both increased cravings and self-administration of the drug (relapse)

Place conditioning Rats confined to one half of a box and given a drug – experience the drug in that location When given opportunity to wander, spend more time in end of the box associated with reinforcing drugs – good indicator of reinforcing value of drug

Second-order schedules First order (FR) is when reward is given after a certain number of responses Second order is given in response to a FR Example: Mouse presses a bar 20 times (FR20) to get a light to turn on – After light is lit 10 times (second order), they get reward of heroin injection – 200 injections total

Final Question Using the positive reinforcement model, explain why nonhuman species avoid the hallucinogen LSD?