Effects of Drugs in an Animal Model of Relapse

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DESCRIPTION: (provided by the applicant) Relapse is a persistent problem in treatment of drug dependence. Although individuals who abuse drugs may achieve periods of abstinence, they frequently reinitiate drug use. Often, relapse is precipitated by brief exposure to the drug that results in loss of control and return to regular drug use. The drug self-administration reinstatement procedure is an important animal model of relapse. Animals first learn to self-administer a drug, and then the opportunity for drug deliveries is removed. Re-exposure to the drug produces reliable reinstatement of extinguished drug seeking. Although this procedure has provided important advances in the understanding of relapse, the process by which drugs reinstate extinguished behavior is not clear. The incentive motivational account, an influential model of relapse, maintains that presentations of a rewarding stimulus such as a drug increase the organism's motivation to acquire that stimulus. Other possible mechanisms of reinstatement, however, are difficult to assess because the drug may have several simultaneous effects that cannot be disentangled in the drug self-administration procedure. In addition to functioning as reinforcers, drugs may also function as signals (discriminative stimuli) for drug availability. Drugs could also produce direct (unlearned and unspecific) rate-increasing effects on behavior unrelated to the reinforcing effects. Examining the role of drugs in reinstating behavior maintained by food separates the reinforcing, discriminative, and direct effects of drugs because the function of the drug as a reinforcer is removed. The proposed experiments will evaluate whether drug-induced reinstatement is specific to behavior maintained by drugs by examining 1) the discriminative effects and 2) the direct effects of drugs in reinstating extinguished behavior previously maintained by food. Experiment 1 will examine the reinstating effects of the psychomotor stimulant cocaine and Experiment 2 will examine the reinstating effects of the opiate morphine. In summary, successful maintenance of abstinence is critical to the health and well being of former drug users. The proposed experiments will help to elucidate the various mechanisms involved in reinstatement to provide the basis for the development of better behavioral and pharmacological treatments to prevent relapse to drug abuse.