Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen
Sex Differences in Selecting Between Food and Cocaine Reinforcement are Mediated by Estrogen
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DOI：
10.1038/npp.2012.99
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发表时间：
2012-11-01
影响因子：
7.6
通讯作者：
Kippin, Tod E.
中科院分区：
文献类型：
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作者：
Kerstetter, Kerry A.;Ballis, Maya A.;Kippin, Tod E.
与男性相比，依赖可卡因的女性报告无可卡因期较短，报告从首次使用到进入成瘾治疗的过渡速度较快。同样，临床前研究表明，雌性大鼠，特别是那些处于生殖周期发情期的雌性大鼠，在各种时间表下对可卡因表现出增加的操作性反应。做出不适应的选择是药物依赖的一个组成部分，同时检查可卡因选择的强化时间表提供了人类药物使用条件的动物模型；因此，研究决策中的性别差异可能对理解为什么女性比男性表现出更严重的可卡因成瘾状况至关重要。因此，我们评估了男性、女性（自由循环）和卵巢切除（OVX）女性在选择食物（45毫克颗粒）和静脉注射可卡因（每次输注0.4或1.0毫克/公斤）强化时的性别和发情周期差异，这些女性接受苯甲酸雌激素（EB；每天5毫克）或载体治疗。在两种可卡因剂量下，完整的雌性大鼠比雄性大鼠更倾向于选择可卡因而不是食物。然而，在完整的雌性中，发情周期并不影响可卡因的选择水平。然而，与每天接受EB治疗的OVX雌性或完整雌性相比，接受载体治疗的OVX雌性表现出明显较低的可卡因选择。这些结果表明，与男性相比，完整的女性更喜欢可卡因而不是食物。此外，这种较高的偏好依赖于雌激素，但在整个女性生殖周期中没有变化，这表明卵巢激素调节了可卡因的选择。目前的研究结果表明，女性有放弃食物强化以获得可卡因强化的生物学倾向，这可能在很大程度上导致女性比男性经历更严重的可卡因成瘾。神经精神药理学（2012）37,2605-2614；doi: 10.1038 / npp.2012.99;2012年8月8日在线发布
Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 mu g per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men. Neuropsychopharmacology (2012) 37, 2605-2614; doi:10.1038/npp.2012.99; published online 8 August 2012