4/28/11: Drugs & Behavior Psych Neurobiological Hypothesis of Drug Abuse: DA Hypothesis of Reward: Researchers and clinicians have many hypotheses and theoretical approaches to try to explain drug abuse/ dependence/ addiction. Some are behavioral (e.g. explanation in terms of personality characteristics like ?sensation-seeking?). Some approaches are neurobiological. For several years, the main neurobiological approach to drug abuse and addiction has been the dopamine hypothesis of reward. According to this hypothesis, DA transmission in nucleus accumbens directly mediates the natural reinforcing effects of food, water, and sex. This so-called ?natural reinforcement system? is said to be turned on by drugs. Neurobiological Hypothesis of Drug Abuse: DA Hypothesis of Reward Evidence: Cited evidence in favor of hypothesis: Drugs of abuse elevate DA in accumbens. Accumbens DA depletions block self- administration in animals. Interference with DA is said to produce ?extinction? (withdrawal of reward) or reduce appetite for natural stimuli such as food. DA antagonists block place preference. However .. there also is evidence that is not consistent with this hypothesis. Problem with cited evidence: Drugs of abuse elevate DA in accumbens. But do stressful stimuli, including benzodiazepine inverse agonists that are anxiogenic. Accumbens DA depletions block self-administration in animals. That is mainly true of stimulants .. with other drugs of abuse that is not true. Interference with DA is said to produce ?extinction? (withdrawal of reward) or reduce appetite. A number of studies have shown that interfering with DA does not produce effects that resemble extinction or loss of appetite: Depleting accumbens DA leaves appetite intact, but animals do work less for food. DA antagonists block place preference learning. But they also block place aversion learning. More problems: Drug abuse in addicts is highly robust. Several recent papers show that the subjective euphoria, or ?high?, or consumption of various drugs of abuse is not blocked by DA antagonists in humans. Drug Abuse is much more complicated than this simple hypothesis would allow. Alternative Neurobiological Theory: It is too simplistic to maintain that all reinforces, including all drugs of abuse, are acting by turning on DA systems. Food reinforcement and drug reinforcement are different. Perhaps different drug effects have different neurochemical substrates: Used and abused drugs tend to be sedatives, stimulants, or drugs that alter sensory processes such as hallucinogens. There may be 3 different systems: Major Stimulants: DA Sedatives/anxiolytics: GABA and endogenous opiates Hallucinogens/alter sensation: 5-HT Additional Hypotheses: Genetic factors: there is substantial genetic predisposition for drug abuse; problem identifying specific genetic factors. ?Psychostimulant? hypothesis. Anxiolytic effects: Incentive-Sensitization hypothesis: sensitization for ?wanting? or ?craving? of drug. Mixture of Positive & Negative Reinforcement: Importance of dependence and withdrawal. Opponent-Process Theory Study Questions for Final:
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