COCAINE'S EFFECTS ACROSS THE MENSTRUAL CYCLE

基于实验室和临床的数据都表明存在差异。 在男性和女性可卡因使用者之间。不幸的是，人类数据 稀疏性和结果因实验室和诊所而异。与女性不同 大鼠、雌性恒河猴的月经周期非常相似 在持续时间和荷尔蒙变化上与人类周期有关。这项提案的目标是 是开发模型来研究增强和区别作用 恒河猴月经周期中的可卡因及其相互关系 性激素状态的变化。我们将跟踪女性的月经周期状况 通过收集每日水平的雌二醇和黄体酮。 建议的研究有5个目标：1)确定单独和 多剂量可卡因对黄体生成素(LH)、皮质醇(CORT)和 整个月经周期的可卡因血浆水平、心率和食物摄入量； 2)确定静脉注射可卡因的增强效果，使用 跨月经周期的累进比例自我给药程序；3) 确定急性胰岛素诱导低血糖(IIH)的影响， 降低黄体生成素和皮质醇在大多数周期阶段，在增强和 可卡因对月经周期的内分泌影响；以及4)决定 可卡因增强功效的周期模式类似于 可卡因的辨别性刺激效应在全国各地的周期性模式 月经周期。将在月经的多个阶段收集数据 雌性在多个时间点循环，雄性在多个时间点。 在拟议的研究中，我们将充分描述加固的特征，以及 可卡因对正常人群月经周期的辨别作用 骑自行车的成年雌性恒河猴和完好无损的雄性。影响的变化 贯穿月经周期的可卡因将与性激素状况有关。这个 拟议的研究将是第一次系统地评估这些影响 非人灵长类动物。结果将澄清一个文学领域，这个领域是在 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研究中的循环。

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.