BEHAVIORAL-EFFECTS OF ACUTE AND CHRONIC COCAINE ADMINISTRATION IN MALE AND FEMALE RATS - EFFECTS OF FIXED-RATIO SCHEDULE PARAMETERS

Intact and gonadectomized male and female rats pressed a lever to obta in food on different fixed-ratio (FR) schedules in a three component m ultiple schedule. The values of a small, intermediate and large FR sch edule were individually determined and were higher for intact male rat s than for most subjects in the other groups. Acute cocaine administra tion (1.0-30.0 mg/kg) dose dependently decreased response rates mainta ined by all three schedules, but responding maintained by the large FR schedule was more sensitive to the rate-decreasing effects of acute c ocaine administration. Response rates of intact male rats were less se nsitive to the rate-decreasing effects of cocaine than those of the ot her groups, at least at higher doses during the small and intermediate FR schedules. Cocaine's dose-effect curve was redetermined after chro nic administration of a behaviorally active dose of cocaine. Differenc es between groups of subjects were not evident. Behavioral tolerance w as consistently observed when responding was maintained by the small F R schedule. Effects varied between subjects within groups when respond ing was maintained by the intermediate FR schedule, but behavioral tol erance was frequently observed. Behavioral sensitization was evident d uring the large FR schedule, but these data were difficult to interpre t because of a considerable shift in response rates after vehicle admi nistration. The data suggest that the comparison of drug effects in ma le and female rats requires a systematic analysis of the contribution of behavioral parameters. They also provide additional evidence for th e notion that reference to reinforcement-loss alone is not sufficient to explain the development of tolerance to the behavioral effects of c ocaine.