Molecular mechanisms of drug reinforcement and addiction.

Abstract

Drug reinforcement is a form of behavioral plasticity in which behavioral changes occur in response to acute exposure to a reinforcing drug. Drugs are classified as reinforcers if the probability of a drug-seeking response is in­ creased when the response is temporally paired with drug exposure. Such rapid and powerful associations between a drug reinforcer and a drug-seeking re­ sponse probably reflect the drug's ability to directly modulate preexisting brain-reinforcement systems. These preexisting systems normally mediate the reinforcement produced by natural reinforcers such as food, sex, and social interaction. Upon acute exposure most abused drugs function as positive rein­ forcers, presumably because they produce a positive affective state (e.g. eu­ phoria). Chronic exposure to reinforcing drugs can lead to drug addiction, which is also characterized by an increase in drug-seeking behavior. Clinically, this sustained increase in drug-seeking behavior (Le. craving) is a core feature of drug addiction. However, unlike drug reinforcement in nonaddicted subjects, addicted subjects exhibit a sustained increase in drug-seeking behavior even when the drug is absent or withdrawn. In some of these situations drugs can function as negative reinforcers in that they offer relief from a negative affec­ tive state (e.g. dysphoria). Since acute drug reinforcement and the addicted state are both characterized by an increase in drug-seeking behavior, common