Sleep and Nocturnal Endocrine Function in MDMA User

描述（由申请人提供）：（+/-）3,4-亚甲基二氧基甲基苯丙胺（MDMA，“摇头丸”）是一种日益流行的滥用精神活性药物，已被证明是动物脑5-羟色胺（5-HT）神经毒素。娱乐性MDMA使用者中越来越多的证据表明，MDMA也会导致人体5-羟色胺损伤。最近非人类灵长类动物的数据表明，一些MDMA使用者（即那些在“狂欢”方案中使用MDMA的人）也可能引起脑多巴胺（DA）神经毒性，尽管尚未进行临床研究来测试这种可能性。MDMA神经毒性对人类的功能影响一直难以确定。然而，一些研究已经证明，先前暴露于MDMA的个体会改变睡眠模式和内分泌功能。由于5-HT和DA参与调节睡眠和内分泌功能，MDMA使用者睡眠和内分泌功能的改变可能与MDMA诱导的5-HT和/或DA神经毒性有关。此外，由于睡眠和昼夜节律影响激素分泌（反之亦然），MDMA使用者的睡眠和内分泌功能异常可能是相互关联的。本研究旨在扩展以往MDMA使用者睡眠和神经内分泌功能的研究，并探索MDMA使用者和匹配对照者睡眠和夜间神经内分泌功能之间可能的相互关系。该项目的具体目的是：1)使用标准的多导睡眠图和频谱功率方法分析两组MDMA使用者和两组匹配的对照受试者的睡眠模式。一组MDMA使用者将是“暴食者”，而第二组将报告从未服用超过每12小时剂量的MDMA。一个控制组将与非MDMA药物使用（除了其他人口统计学变量）的MDMA使用者相匹配，而第二组控制组将没有非法药物滥用史。2)表征夜间泌乳素、生长激素和皮质醇（受睡眠影响的5-羟色胺和/或DA调节的三种激素）的分泌模式；3)在影响内分泌分泌的环境和认知因素最小的情况下，对男性和女性MDMA使用者在睡眠期间使用间氯苯哌嗪（m-CPP）进行5-HT药理挑战。拟议研究的结果将有助于更好地定义MDMA暴露在人体中的功能后果，并可能阐明5-羟色胺和DA在睡眠和夜间内分泌功能中的作用。

DESCRIPTION (provided by applicant): (+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is an increasingly popular psychoactive drug of abuse that has been shown to be a potent brain serotonin (5-HT) neurotoxin in animals. Growing evidence in recreational MDMA users indicates that MDMA can also lead to 5-HT damage in humans. Recent data in non-human primates suggests that some MDMA users (i.e., those who use MDMA in a "binge" regimen) may also incur brain dopamine (DA) neurotoxicity, although clinical studies to test this possibility have not yet been conducted. Functional consequences of MDMA neurotoxicity in humans have been difficult to identify. However, several studies have demonstrated altered sleep patterns and endocrine function in individuals previously exposed to MDMA. Since 5-HT and DA are involved in the regulation of sleep and endocrine function, it is possible that altered sleep and endocrine function in MDMA users is related to MDMA-induced 5-HT and/or DA neurotoxicity. Further, since sleep and circadian rhythms influence hormonal secretion (and vice versa), abnormalities of sleep and endocrine function in MDMA users may be inter-related. The proposed studies are intended to extend previous studies of sleep and neuroendocrine function in MDMA users, and explore possible interrelations between sleep and nocturnal neuroendocrine function in MDMA users and matched controls. The specific aims of the project are: 1) To analyze sleep patterns of 2 groups of MDMA users and 2 groups of matched control subjects using standard polysomnographic and spectral power methods. One group of MDMA users will be "bingers," whereas the second group will report never having taken more than dose of MDMA dose per 12-hour period. One control group will be matched with MDMA users for non-MDMA drug use (in addition to other demographic variables) whereas the second group of controls will have no history of illicit drug abuse. 2) To characterize the nocturnal secretion patterns of prolactin, growth hormone, and cortisol, three hormones that are modulated by 5-HT and/or DA influenced by sleep; and 3) To conduct 5-HT pharmacological challenges with m-chlorophenylpiperazine (m-CPP) in male and female MDMA users during sleep, when environmental and cognitive factors that can influence endocrine secretion are minimal. Results from the proposed studies will help better define the functional consequences of MDMA exposure in humans, and could shed light on the roles of 5-HT and DA in sleep and nocturnal endocrine function.