Progesterone and allopregnanolone are induced by cocaine in serum and brain tissues of male and female rats.

Acute and chronic-cocaine administration increase serum levels of progesterone in both male and female rats. This study aimed to determine whether progesterone and its bioactive metabolite allopregnanolone (ALLOP) are altered in the hippocampus and striatum (areas known to modulate cocaine-induced behavioral response) after acute cocaine administration. To this end, male and female rats were administered 20 mg/kg and 5 mg/kg of cocaine, respectively (doses that produce equivalent behavioral responses between the sexes). Thirty minutes after drug treatment, serum and brain were collected and later analyzed for progesterone and ALLOP levels using HPLC measurements. At these cocaine doses, no sex differences in the overall behavioral responses after drug treatment were observed. In saline-treated controls, female rats had overall higher levels of progesterone in the serum than did male rats. After cocaine administration, progesterone and ALLOP levels in serum, hippocampus, and striatum were increased at similar levels in both sexes. In the hippocampus, progesterone levels were increased in both males and females, but ALLOP levels were increased only in females.

Progesterone attenuates cocaine-induced conditioned place preference in female rats.

Progesterone replacement attenuates the intensity of cocaine-induced conditioned place preference (CPP) behaviors in female rats. The present study aimed to expand that finding by (i) determining the role of progesterone in the acquisition and/or expression of cocaine-induced CPP and (ii) determining if progesterone's effects might be meditated through learning and memory. To this end, female rats were administered progesterone during cocaine conditioning or object recognition tasks; rats received subcutaneous injections of progesterone (500 microg) or vehicle (sesame oil) 4 h before saline or cocaine (5 mg/kg) on conditioning days (acquisition phase) or before testing (expression phase or object recognition tasks). Progesterone treatment during both the acquisition and the expression phases of cocaine conditioning blocked cocaine-induced CPP. Progesterone affected neither the number of entrances and explorations in the CPP chambers nor the ambulatory and rearing behaviors. In the object recognition task (a non-spatial learning and memory task), progesterone treatment had no effect. However, in the object placement task (a spatial learning and memory task), progesterone treatment significantly impaired retention in hormone-treated rats as compared with control groups. These results suggest that progesterone treatment interferes with cocaine-induced reward associations, possibly through effects on spatial working memory consolidation The observed effects of acute progesterone treatment on cocaine-induced CPP may in part contribute reported menstrual effects and sex disparities in overall cocaine use and rates of relapse.