Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques
Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques
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DOI：
10.1016/j.yhbeh.2012.10.008
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发表时间：
2013-01-01
影响因子：
3.5
通讯作者：
Evans, Suzette M.
中科院分区：
文献类型：
--
作者：
Cooper, Ziva D.;Foltin, Richard W.;Evans, Suzette M.
流行病学调查结果表明，男子和妇女使用可卡因的方式不同，导致可卡因依赖和复发率不同。临床前实验室研究表明，雌性啮齿动物确实对可卡因的增强作用比雄性更敏感，发情周期阶段是这种作用的关键决定因素。目前的研究试图将这些发现扩展到正常循环的雌性恒河猴，这种物种与人类的月经周期几乎相同。在整个月经周期中，采用递增比例强化方案确定剂量依赖性静脉内可卡因自我给药（0.0125、0.0250和0.0500 mg/kg/输注）。月经周期分为5个离散阶段-月经期、卵泡期、排卵期、黄体期和黄体晚期-通过月经开始和血浆雌二醇和孕酮水平进行验证。根据可卡因剂量和月经周期阶段分析因变量，包括每次自我给药的输注次数、渐进比率断点和可卡因摄入量。血浆激素水平的分析证实了雌二醇和孕酮的阶段依赖性波动，雌激素水平在排卵期达到峰值，孕酮在黄体期达到峰值。渐进比例断点，输液自我管理，可卡因摄入量并没有一贯不同的基础上月经周期阶段。这些发现表明，在目前的实验参数下，可卡因的强化作用在正常循环的恒河猴中在整个月经周期中没有系统性的变化。(c)2012 Elsevier Inc. All rights reserved.
Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. (c) 2012 Elsevier Inc. All rights reserved.