Sleep and Nocturnal Endocrine Function in MDMA User

描述（由申请人提供）： （+/-）3，4-亚甲二氧基甲基苯丙胺（MDMA，“摇头丸”）是一种越来越受欢迎的滥用精神活性药物，已被证明是动物脑中的一种强效5-羟色胺（5-HT）神经毒素。越来越多的娱乐性MDMA使用者的证据表明，MDMA也可能导致人类5-HT损伤。最近在非人类灵长类动物中的数据表明，一些MDMA使用者（即，那些在“狂欢”疗法中使用MDMA的人）也可能引起脑多巴胺（DA）神经毒性，尽管尚未进行测试这种可能性的临床研究。MDMA神经毒性对人体的功能影响一直难以确定。然而，一些研究表明，以前接触过MDMA的人的睡眠模式和内分泌功能发生了改变。由于5-HT和DA参与睡眠和内分泌功能的调节，因此MDMA使用者的睡眠和内分泌功能改变可能与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相互关联。拟议的研究旨在扩展MDMA使用者的睡眠和神经内分泌功能的先前研究，并探索MDMA使用者和匹配对照者的睡眠和夜间神经内分泌功能之间可能的相互关系。本研究的具体目的是：1）采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者的睡眠模式。一组MDMA使用者将是“暴食者”，而第二组将报告每12小时内从未服用超过剂量的MDMA。一个对照组将与MDMA使用者进行非MDMA药物使用（除其他人口统计学变量外）匹配，而第二组对照组将没有非法药物滥用史。2)描述催乳素、生长激素和皮质醇（受睡眠影响的5-HT和/或DA调节的三种激素）的夜间分泌模式;以及3）在睡眠期间，当可影响内分泌的环境和认知因素最小时，用间氯苯基哌嗪（m-CPP）对男性和女性MDMA使用者进行5-HT药理学激发。拟议研究的结果将有助于更好地确定人类暴露于MDMA的功能后果，并可能揭示5-HT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.