COCAINE'S EFFECTS ACROSS THE MENSTRUAL CYCLE

实验室和临床数据都表明， 男性和女性可卡因使用者之间的差异。不幸的是，人类的数据 结果在实验室和诊所之间存在差异。与女性相比， 大鼠雌性恒河猴的月经周期与 与人类周期的持续时间和荷尔蒙变化有关。这项提案的目的是 是开发模型来研究的强化和歧视的影响， 可卡因在恒河猴月经周期中的作用， 性激素状态的变化。我们将跟踪女性的月经周期状态 通过每天收集雌二醇和孕酮的水平。 本研究有5个目的：1）确定单一和 多剂量可卡因对促黄体生成激素（LH）、皮质醇（CORT）和 可卡因血浆水平，心率和整个月经周期的食物摄入量; 2)确定静脉注射可卡因的强化作用，使用 渐进比例自我给药程序，跨月经周期; 3） 确定急性胰岛素诱导的低血糖（IIH）的影响， 在大多数周期阶段，LH降低，CORT升高， 可卡因对整个月经周期的内分泌影响;以及4）确定是否 可卡因增强效力的周期性模式与 可卡因在整个大脑中的辨别性刺激效应的周期性模式 月经周期将在月经的多个阶段收集数据 雌性动物在周期中，雄性动物在多个时间点。 在拟议的研究中，我们将充分表征强化， 可卡因在正常月经周期中的辨别作用 骑自行车的成年雌性恒河猴和完整的雄性。影响的变化 可卡因在整个月经周期将与性激素的状态。的 拟议的研究将是第一个系统地评估这些影响的研究， 非人类灵长类动物结果将澄清一个领域的文献，是在 混乱，部分原因是未能充分控制月经 在人类和非人类灵长类动物的研究中，

Both laboratory-based and clinical data suggest that differences exist between male and female cocaine users. Unfortunately, the human data are sparse and results vary across laboratories and clinics. In contrast to female rats, female rhesus monkeys have menstrual cycles that are remarkably similar to human cycles in duration and hormonal variations. The goal of this proposal is to develop models for studying the reinforcing and discriminative effects of cocaine across the menstrual cycle in rhesus monkeys and to relate these changes to sex hormone status. We will track menstrual cycle status in females by collecting daily levels of estradiol and progesterone. The proposed research has 5 objectives: 1) determine the effects of single and multiple-doses of cocaine on luteinizing hormone (LH), cortisol (CORT) and cocaine plasma levels, heart rate and food intake across the menstrual cycle; 2) determine the reinforcing effects of intravenous cocaine, using a progressive-ratio self-administration procedure, across the menstrual cycle; 3) determine the effects of acute insulin-induced hypoglycemia (IIH), which decreases LH and increases CORT at most cycle phases, on the reinforcing and endocrine effects of cocaine across the menstrual cycle; and 4) determine if the cyclical pattern in the reinforcing efficacy of cocaine is similar to the cyclical pattern in the discriminative stimulus effects of cocaine across the menstrual cycle. Data will be collected at multiple phases of the menstrual cycle in females and at multiple time points in males. In the proposed studies, we will fully characterize the reinforcing, and discriminative effects of cocaine across the menstrual cycle in normally cycling adult female rhesus monkeys and intact males. Changes in the effects of cocaine across the menstrual cycle will be related to sex hormone status. The proposed studies will be the first to systematically evaluate these effects in non-human primates. The results will clarify an area of literature that is in disarray, in part because of the failure to adequately control for menstrual cycle in studies with human and non-human primates.