Ovarian hormone replacement affects cocaine-induced behaviors in ovariectomized female rats

To determine whether cocaine-induced behavioral alterations are modulated by ovarian hormones, ovariectomized rats were randomly assigned to one of two drug treatment conditions: "binge" cocaine (three 15-mg/kg intraperitoneal (ip) injections, 1 h apart) or saline administration; and four hormone pretreatment sub-groups: vehicle control, estrogen, progesterone, or estrogen+progesterone. Cocaine-treated animals displayed more locomotor activity than saline-treated animals and locomotor activity was higher after the third injection than after the first two injections. When analyzed according to hormone group, the administration of estrogen+progestrone suppressed cocaine-induced locomotion after the first injection; this effect was significant when compared to estrogen-pretreated animals. While in each condition cocaine-treated animals displayed significantly higher stereotypic activity than saline-treated animals, in the estrogen+progesterone replacement group, there was more activity after the second injection of cocaine than after the first. Interestingly, animals in the estrogen+progesterone group had significantly lower plasma levels of the cocaine metabolite, benzoylecgonine, than animals in the progesterone or estrogen groups. These results extend our earlier findings in the intact female rat, which suggest an interaction between the endocrine environment, cocaine metabolism, and cocaine-induced behaviors. These effects may underlie reported sex and estrous cycle differences in cocaine-induced behavioral activity.