Niyomchai Tipyamol, Russo Scott J, Festa Eugene D, Akhavan Alaleh, Jenab Shirzad, Quiñones-Jenab Vanya
Department of Psychology, Hunter College of the City University of New York and Subprogram in Biopsychology, Graduate School and University Center of the City University of New York, New York, NY 10021, USA.
Pharmacol Biochem Behav. 2005 Apr;80(4):603-10. doi: 10.1016/j.pbb.2005.01.010.
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.
越来越多的证据表明，雌激素和孕酮会导致对可卡因产生性别差异的行为反应。在本研究中，我们检验了以下假设：改变雌激素或孕酮水平会影响雌性大鼠中可卡因诱导的运动行为。去卵巢（OVX）大鼠在急性给予生理盐水或可卡因（15mg/kg）前48小时接受雌激素（0、5、10、20或50微克）或24小时前接受孕酮（0、50、100、250或500微克）。尽管雌激素不影响可卡因诱导的走动和竖毛行为，但无论是否给予可卡因，它都会影响刻板行为（接受50微克雌激素的动物的刻板行为计数高于OVX组）。相比之下，孕酮对竖毛活动有剂量依赖性影响：50微克和500微克的孕酮会抑制，而100微克和250微克的孕酮会刺激对可卡因的竖毛反应。雌激素和孕酮不影响总体基线行为活动，这表明它们的作用部分是通过与可卡因的相互作用介导的。给予孕酮不影响生理盐水或可卡因处理大鼠的皮质酮水平。然而，给予雌激素会影响基线和可卡因处理后的皮质酮水平。在考虑基线差异后，我们发现接受5微克或10微克雌激素和可卡因的大鼠血清皮质酮水平的百分比增幅高于未接受雌激素的对照组。基于这些观察结果，我们认为发情周期中孕酮的波动会影响可卡因诱导的行为反应，而雌激素可能会影响下丘脑-垂体-肾上腺轴的活动。因此，性腺激素的剂量依赖性作用可能是可卡因所报告的一些性别差异和生殖周期效应的基础。
