Cocaine abuse is one of the most important problems facing American society today. Recent years have seen a steady stream of research reports documenting the effects of behaviorally active doses of cocaine, both after acute and chronic administration. However, most of the behavioral effects of cocaine have been established in male subjects only. Relatively little research effort has been directed at investigating the behavioral effects of acute and repeated cocaine administration in females, despite the fact that evidence is available to suggest that gonadal hormones may differentially affect the behavioral effects of psychomotor stimulants, including cocaine. The long-term objective of this proposal is to analyze the role of endogenous gonadal hormones in modifying the behavioral effects of acute and repeated cocaine administration in male and female rats. It is important to identify the way in which gonadal hormones modify the behavioral effects of acute and repeated cocaine administration because of the fact that this information may be essential to the design of proper (gender-dependent) treatment and prevention strategies. Specific attention will be paid to the behavioral effects of relatively small doses of acute cocaine administration on voluntary behavior maintained by different schedules of reinforcement. Because of the fact that repeated cocaine administration may result in behavioral tolerance or sensitization to the effects of subsequent cocaine intake, schedule-controlled behavior of intact and gonadectomized male and female rats will be investigated after repeated cocaine exposure. The discriminate-stimulus properties of cocaine will also be examined in an attempt to identify some of the variables which may be responsible for cocaine's differential effects on behavior in male and female rats. Finally, the behavioral effects of withdrawal from repeated cocaine administration will be analyzed to shed more light on the variables which maintain 'drug seeking' after repeated cocaine administration, in male and female rats.
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