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，只有有限数量的啮齿动物研究评估了阿片类药物的增强作用是否存在性别差异，而且人类数据很少。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。这项建议将对正常周期的成年雌性恒河猴在整个月经周期内吸烟海洛因的行为和强化效果进行参数评估，并定期监测雌二醇(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影响联系起来。实验1将仔细描述海洛因血浓度在整个月经周期中的时间进程。随后，在猴子不依赖的情况下，将使用二级时间表、选择和地点偏好程序来衡量寻找和服用海洛因(实验。2)和再一次(实验4)当他们依赖阿片类药物时；当猴子不依赖时，将使用累进比率程序来衡量海洛因的增强效果(实验。3)和再次(例5)当他们依赖阿片类药物时。这些实验将提供有价值的数据，说明海洛因在非依赖和依赖条件下可用时，在整个月经周期内的行为和强化效果的变化。此外，该提案将提供有关自我给药阿片类药物对月经周期调节的影响的重要信息。这项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.