Cocaine is used regularly by more than two million Americans. These people administer the drug to themselves repeatedly. Development of effective preventive and treatment strategies, therefore, will be aided by a clear understanding of the effects of repeated exposure to cocaine. Laboratory research on effect of repeated cocaine administration has revealed that the outcome of such exposure can be either increased sensitivity to the drug's effects (sensitization) or decreased sensitivity to its effects (tolerance). At present, variables responsible for determining whether sensitization or tolerance develops as a consequence of repeated cocaine administration have not been identified clearly. The research proposed in this application will help identify factors that may play a role in determining the effects of repeated exposure to cocaine. It has been shown clearly that behavioral factors can modulate effects of repeated cocaine administration, and one focus of the proposed research will be to attempt to isolate precisely behavioral variables that influence effects of chronic cocaine administration. Specifically, variables that are known to motivate operant performance, e.g., deprivation and reinforcement magnitude, will be tested, as will characteristics of reinforcement contingencies that have been implicated in previous research. Surprisingly, two other factors have received virtually no experimental attention: Dose and frequency of drug administration. Systematic assessment of the contributions of dose magnitude and frequency of exposure to effects of repeated cocaine administration is proposed.
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