Influence of ovarian hormones and estrous cycle on the behavioral response to cocaine in female rats

Both humans and experimental animals demonstrate gender differences in response to cocaine. However, the mechanisms underlying these differences remain unclear. The purpose of the present study was to determine whether ovarian steroid hormones play a role in the locomotor response to cocaine in rats. Initial assessments of locomotor activity measured using photobeam monitors verified the robust gender difference in response to cocaine in our experimental paradigm. Subsequently, cocaine (5.0, 7.5, and 10.0 mg/kg) was shown to increase total horizontal activity in a dose-dependent manner in independent groups of intact females; the 5.0 mg/kg dose was selected for use in additional studies to determine the effect of estrogen (E) and progesterone (P) on the response to cocaine. Mature female rats were ovariectomized (OVX) or OVX and implanted with hormone-filled (E or P) Silastic capsules. Three to 4 weeks later, automated and observational measures of behavior were recorded after the administration of 5 mg/kg cocaine. Hormone replacement with E or E + P (but not P alone) resulted in greater cocaine-evoked hyperactivity than was observed in OVX animals. On measurement in normally cycling rats, hyperactivity induced by 5 mg/kg cocaine was greater during proestrus and estrus than during diestrus 2. The results of this series of experiments demonstrate that E significantly influences the responsiveness of female rats to cocaine. The enhanced response to cocaine was demonstrated in the presence of pharmacologically administered E as well as correlated with the normal estrous cycle.