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，对药物滥用的反应存在性别差异。然而，只有有限数量的啮齿动物研究评估了阿片类药物的强化效应是否存在性别差异，而人类的数据很少。然而，观察到的一些性别差异可以归因于女性卵巢激素的循环。本研究将对正常月经周期的成年雌性恒河猴吸食海洛因的行为和强化效应进行参数化评估，常规监测雌二醇（EST）、黄体酮（PRO）和黄体生成素（LH）水平，将激素水平的变化与海洛因的行为影响联系起来。实验1将仔细描述海洛因在月经周期中的血药浓度的时间过程。随后，当猴子不依赖阿片类药物时（实验2），当它们依赖阿片类药物时（实验4），将使用二级时间表、选择和位置偏好程序来测量海洛因的寻找和服用；当猴子不依赖阿片类药物时（实验3）和依赖阿片类药物时（实验5），将使用递进比程序测量海洛因的强化效应。这些实验将提供有关海洛因在非依赖和依赖条件下在整个月经周期中行为变化和强化效应的宝贵数据。此外，该提案将提供关于自我给药阿片类药物对月经周期调节的影响的重要信息。拟议的研究将首次系统地评估这些对雌性非人类灵长类动物的影响。

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.