[show abstract][hide abstract] ABSTRACT: The present study aimed to determine if, as occurs in female rats, progesterone attenuates cocaine-induced reward and psychomotor responses in male rats.
The role of progesterone in the acquisition and/or expression of cocaine-induced conditioned place preference (CPP) and locomotor responses of intact male rats was studied. For chronic progesterone treatment, rats received Silastic capsules with either progesterone (100%) or vehicle 1 week prior to conditioning. For acute progesterone treatment, rats received subcutaneous injections of progesterone (500 microg) or vehicle (sesame oil) 4 hours before intraperitoneal injections of saline or cocaine administration (20 mg/kg) on conditioning days (acquisition phase-formation of reward associations) or before testing (expression phase-recall of reward associations).
Both progesterone-treatment paradigms produced equivalent progesterone serum levels. Progesterone administered chronically or acutely during the acquisition and expression phases of cocaine conditioning did not block cocaine-induced CPP. Nor did progesterone affect ambulatory or rearing behaviors after cocaine administration.
These results suggest that, unlike the findings with female rats (in which similar treatment paradigms inhibited the formation and recall of cocaine-induced CPP), progesterone plays a limited role in the cocaine-induced reward or psychomotor responses of male rats.
[show abstract][hide abstract] ABSTRACT: 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.
Brain Research 02/2008; 1189:229-35. · 2.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Growing evidence suggests that sex differences in cocaine reward responses are regulated by endogenous gonadal hormones. However, few studies have addressed the role of testosterone on cocaine reward and psychomotor activation. This study aimed to determine whether testosterone influences the development of psychomotor and reward responses to cocaine. Castrated 8-week-old male Fisher rats received placebo or testosterone via Silastic capsules (1-3 capsules of 100% testosterone) or subcutaneous injections (400, 800, or 1200 microg/kg) concurrent with cocaine administration. Although chronic testosterone administration did not alter cocaine-induced conditioned place preference (CPP), concurrent administration of testosterone and cocaine affected the development of cocaine CPP dose-dependently; 400 microg/kg blocked the expression of cocaine-induced CPP. Testosterone did not affect cocaine-induced locomotor activity. Furthermore, testosterone-saline-treated controls did not develop CPP, suggesting that at these doses, testosterone does not produce rewarding or motor responses. These data suggest that testosterone may play a limited role in cocaine-induced reward associations and locomotor responses and thus has a limited effect in the previously reported sexually dimorphic responses to cocaine.
[show abstract][hide abstract] ABSTRACT: It is well established that there are estrous cycle differences in cocaine-induced behavioral activity, implicating fluctuations in levels of estrogen and progesterone throughout the cycle in these alterations in behavior. However, the mechanisms by which steroids alter cocaine-induced behavioral responses have yet to be determined. The aim of this study was to determine whether short- or long-term estrogen and progesterone administration differentially alters behavioral responses to cocaine. Estrogen (50 microg) was administered 30 min or 48 h before cocaine (15 mg/kg, i.p.) administration; progesterone (500 microg) was administered 30 min or 24 h before cocaine. Short-term estrogen replacement decreased cocaine-induced ambulations. Short-term progesterone decreased rearing, whereas long-term progesterone decreased ambulations. Although cocaine increased levels of c-fos mRNA, none of the estrogen or progesterone replacement paradigms affected this measure. Because long-term estrogen replacement has been shown to have no effect on locomotor activity after acute cocaine administration, our observations suggest that short-term estrogen may underlie behavioral alterations. These findings suggest that after acute cocaine administration, while estrogen may activate only membrane receptors to alter behavioral responses to cocaine, progesterone activates both nuclear and membrane receptors.
Brain Research 01/2007; 1126(1):193-9. · 2.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although it is established that female rats have a more robust behavioral response to acute cocaine administration than male rats, the neurobiological mechanisms underlying these differences remain unclear. The purpose of the present study was to determine whether dopamine (DA) receptor activation influences sex differences in cocaine-induced behaviors. A second study was performed to determine sex differences in D1/D2 receptor levels prior to and post-cocaine administration. Male and female Fischer rats were pre-treated with the D1 antagonist SCH-23390 (0.05, 0.1, and 0.25 mg/kg, i.p.), the D2 antagonist eticlopride (0.03, 0.1 mg/kg, i.p.), or vehicle (saline) 15 min before acute cocaine (20 mg/kg, i.p.) or saline administration. Cocaine-induced ambulatory and rearing activity was greater in female than male rats. Pre-treatment with SCH-23390 affected cocaine-induced ambulatory, rearing, and stereotypic activity in a sex-dependent manner; cocaine-induced ambulatory and stereotypic behavior in female rats was reduced by the lowest dose of SCH-23390. Eticlopride did not alter behavioral responses to cocaine in male or female rats. These results suggest that in both male and female rats, activation of the D1, but not the D2, receptor modulates cocaine's motor effects. There were no sex differences in baseline levels of D1, D2, and DA transporter binding in the caudate putamen (CPu) and the nucleus accumbens (NAc). Cocaine administration reduced D1 binding levels in the CPu only in male rats. Our findings suggest that the regulation of striatal D1 binding levels after acute cocaine administration is a sexually dimorphic process. We also hypothesize that the greater sensitivity to D1 receptor blockade in female rats, as compared to male rats, may contribute to their overall increased hyperactivity in response to acute cocaine. Taken together, the D1 receptor may be an important substrate in the regulation of sex differences to cocaine-induced locomotor activity.
Brain Research Bulletin 02/2006; 68(4):277-84. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several studies have reported sex differences in behavioral responses to cocaine whereby females display a greater degree of locomotor activity. Fluctuations in estrogen and progesterone during the estrous cycle have been postulated to underlie these behavioral differences. In this study, we tested the hypothesis that hormonal replacement (estrogen or progesterone) in ovariectomized rats affects cocaine pharmacokinetics. We found that estrogen replacement did not affect cocaine-induced locomotor activity, but progesterone attenuated locomotor counts in comparison with control groups receiving only sesame oil. Estrogen, however, decreased brain levels of cocaine and norcocaine 30 min after cocaine administration in comparison to the group-receiving vehicle at that time point. In addition, in progesterone-treated rats, levels of benzoylecgonine and ecgonine methylester were higher at 30 min post-administration than at 15 min. No changes were found in blood levels of the metabolites. These findings suggest that while progesterone has an impact on locomotor behavior, pharmacokinetic effects may have a limited role in mediating behavioral responses to cocaine.
Brain Research Bulletin 02/2006; 68(5):310-4. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.
Pharmacology Biochemistry and Behavior 05/2005; 80(4):603-10. · 2.61 Impact Factor