Acquisition and maintenance of cocaine self-administration in adolescent rats: effects of sex and gonadal hormones

Rationale Previous work has shown that adult female rats are more sensitive than adult male rats to the reinforcing effects of cocaine, an effect that appears to be due, at least in part, to ovarian hormones. Objective In this study, we examine sex differences in cocaine self-administration during adolescence, a period of marked hormonal change. Materials and methods Adolescent male and female Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg per infusion) under a fixed ratio 1 schedule (i.e., each response was reinforced by an infusion of cocaine) beginning on postnatal day 30. After acquisition, responding was assessed under a progressive-ratio schedule until postnatal day 50 with blood sampling occurring before the first five sessions to determine the relationship between gonadal hormones (i.e., estradiol, progesterone, and testosterone) and motivation for cocaine. Estrous cycle phase was monitored throughout the study. Separate groups of adolescent male and female rats were compared on the acquisition of and progressive-ratio responding for sucrose reinforcement. Results Females acquired cocaine self-administration more readily than did males, and a greater percentage of females acquired self-administration. Under progressive-ratio testing conditions, adolescent females responded at higher levels than adolescent males to obtain cocaine infusions, and in females, responding was positively associated with levels of estradiol and greatest during estrus. No sex differences were observed for sucrose reinforcement. Conclusion These findings suggest that sex differences are relevant during adolescence with evidence implicating circulating estradiol level as a factor that contributes to the enhanced sensitivity in females to the reinforcing effects of cocaine.