Effect of Gonadectomy and Gonadal Hormone Replacement on Cocaine Self-Administration in Female and Male Rats

Both sex and gonadal steroid hormones may influence the abuse-related behavioral effects of cocaine under some conditions, but there is considerable inconsistency in the literature. In the present study, rats were trained under a fixed ratio (FR) 5 schedule of food presentation and were then allowed to self-administer cocaine (1.0 mg/kg/injection) until behavior stabilized. Subsequently, complete dose-effect functions for cocaine self-administration (0.032–3.2 mg/kg/injection) were determined in female and male rats before and after gonadectomy, and in gonadectomized female and male rats before and during chronic treatment with estradiol or testosterone, respectively. Sex, gonadectomy, and gonadal hormones did not alter the shape or position of dose-effect functions for cocaine self-administration. These results suggest that sex, estrogen, and testosterone levels are not critical determinants of cocaine's reinforcing effects in rats under these conditions. This study differed from earlier studies in that complete dose-effect functions for cocaine were determined. These findings suggest that the behavioral training history, the unit dose of cocaine, and the schedule of reinforcement are important variables in studies of sex and gonadal hormone effects on cocaine self-administration.