Effects of Smoked Heroin Across the Menstrual Cycle

描述（由申请人提供）：越来越多的证据表明，对滥用药物的反应存在性别差异。然而，只有数量有限的啮齿动物研究评估了阿片类药物的强化作用是否存在性别差异，人类数据也很少。然而，观察到的一些性别差异可归因于女性卵巢激素的循环。该提案将参数化地评估吸烟海洛因在正常周期的成年雌性恒河猴的整个月经周期中的行为和强化作用。将常规监测雌二醇（EST）、孕酮（PRO）和黄体生成素（LH）的水平，将激素水平的变化与海洛因的行为效应相关联。Exp. 1将仔细描述海洛因血液水平在月经周期中的时间过程。随后，当猴子不依赖时，将使用二阶时间表、选择和位置偏好程序来测量海洛因寻求和服用（实验1）。2)再一次（Exp. 4)当它们依赖于阿片类药物时;并且当猴子不依赖时，海洛因的增强作用将使用累进比率程序来测量（Exp. 3)再次（实验5），当他们依赖阿片类药物时。这些实验将提供有关海洛因在非依赖性和依赖性条件下可获得的整个月经周期中海洛因的行为和强化作用的变化的有价值的数据。此外，该提案还将提供关于自行服用类阿片对调节月经周期的影响的重要信息。拟议的研究将是第一个系统地评估这些影响的女性非人类灵长类动物。

DESCRIPTION (provided by applicant): There is growing evidence that there are sex differences in response to drugs of abuse. However, only a limited number of studies in rodents have assessed whether there are sex differences in the reinforcing effects of opioids and the human data are sparse. Nevertheless, some of the sex differences observed can be attributed to cycling ovarian hormones in females. This proposal will parametrically evaluate the behavioral and reinforcing effects of smoked heroin across the menstrual cycle in normally-cycling adult female rhesus monkeys, Levels of estradiol (EST), progesterone (PRO) and luteinizing hormone (LH) will be routinely monitored, correlating changes in hormone levels to the behavioral effects of heroin. Exp. 1 will carefully characterize the time course of heroin blood levels across the menstrual cycle. Subsequently, heroin seeking and taking will be measured using a second-order schedule, choice and location preference procedures when the monkeys are not dependent (Exp. 2) and again (Exp. 4) when they are dependent on opioids; and the reinforcing effects of heroin will be measured using a Progressive Ratio procedure when the monkeys are not dependent (Exp. 3) and again (Exp.5) when they are dependent on opioids. These experiments will provide valuable data about changes in the behavioral and reinforcing effects of heroin across the menstrual cycle when heroin is available under non-dependent and dependent conditions. In addition, this proposal will provide important information on the effects of self-administered opioids on the regulation of the menstrual cycle. The proposed studies will be the first to systematically evaluate these effects in female non-human primates.