Sex differences and hormonal influences on acquisition of cocaine self-administration in rats

Men and women differ in their response to cocaine, and a woman's response varies with the menstrual cycle. For example, women have greater subjective responses to cocaine in the follicular phase of the menstrual cycle when estradiol is predominant, than they do during the luteal phase when both estradiol and progesterone are elevated. Similarly, female rats show significantly more cocaine-induced locomotor behavior and cocaine self-administration during behavioral estrus, shortly after estradiol peaks, than during other stages of the cycle, and estradiol administration to ovariectomized (OVX) females enhances the acquisition of cocaine self-administration. The purpose of this study was to expand upon these findings by studying the effects of progesterone administration to females, and estradiol administration to males, on acquisition of cocaine self-administration. We report here that there are both sex differences in and effects of circulating ovarian hormones on acquisition of cocaine self-administration. We demonstrate that although estradiol administration enhances acquisition of cocaine self-administration in OVX female rats, concurrent administration of progesterone with estradiol inhibits this effect of estradiol. In a separate experiment, we demonstrate that estradiol administration does not enhance acquisition of cocaine self-administration in castrated male rats. We conclude that (1) there is a sex difference in the effects of estradiol on cocaine self-administration: it facilitates acquisition in female, but not male rats; and that (2) in females concurrent progesterone treatment counteracts the facilitory effect of estradiol on cocaine self-administration.