Behavioral effects of acute and chronic cocaine administration in male and female rats: effects of fixed-ratio schedule parameters.

Abstract

Intact and gonadectomized male and female rats pressed a lever to obtain food on different fixed-ratio (FR) schedules in a three-component multiple schedule. The values of a small, intermediate and large FR schedule were individually determined and were higher for intact male rats than for most subjects in the other groups. Acute cocaine administration (1.0-30.0mg/kg) dose-dependently decreased response rates maintained by all three schedules, but responding maintained by the large FR schedule was more sensitive to the rate-decreasing effects of acute cocaine administration. Response rates of intact male rats were less sensitive to the rate-decreasing effects of cocaine than those of the other groups, at least at higher doses during the small and intermediate FR schedules. Cocaine's dose-effect curve was redetermined after chronic administration of a behaviorally active dose of cocaine. Differences between groups of subjects were not evident. Behavioral tolerance was consistently observed when responding was maintained by the small FR schedule. Effects varied between subjects within groups when responding was maintained by the intermediate FR schedule, but behavioral tolerance was frequently observed. Behavioral sensitization was evident during the large FR schedule, but these data were difficult to interpret because of a considerable shift in response rates after vehicle administration. The data suggest that the comparison of drug effects in male and female rats requires a systematic analysis of the contribution of behavioral parameters. They also provide additional evidence for the notion that reference to reinforcement-loss alone is not sufficient to explain the development of tolerance to the behavioral effects of cocaine.