BRAIN SEROTONIN TRANSPORTER IN ECSTASY AND MDA USERS

简介(申请人提供)：背景。动物数据表明，广泛使用的违禁药物摇头丸(MDMA)及其更有效的代谢物丙二醛(以前被称为“爱情药”)会损害大脑中的5-羟色胺神经元。然而，由于实验设计以及用于评估5-羟色胺神经元完整性的放射性标记探针的有效性和可靠性方面的问题，试图测量人类吸毒者大脑5-羟色胺标记物水平的有限体内神经成像研究的结果并不确定。宽广的目标。我们的广泛目标是确定摇头丸和丙二醛对人脑的“伤害”程度。明确的目标、假设和设计。我们主要的特殊目的是通过PET(正电子发射断层扫描)神经成像来确定从我们最近开发的探针[11C]-DASB的结合中推断的5-羟色胺神经元的关键成分--5-羟色胺转运体(SERT)的水平是否在长期服用摇头丸的人和使用丙二醛的人的大脑中与匹配的对照组相比降低。我们的调查包括使用法医毛发分析来明确证明长期使用摇头丸/丙二醛，以及使用由我们的PET中心开发的新的SERT放射性标记探针，它没有与以前的放射性示踪剂相关的有效性/可靠性问题。与健康相关。所获得的数据将为摇头丸和丙二醛(我们相信这种药物将越来越受欢迎)是否会损害人类大脑5-羟色胺神经元的功能提供有用的信息。更广泛地说，我们的数据将有助于确定大脑5-羟色胺系统的不同神经解剖学组件对人类行为的贡献。

DESCRIPTION (provided by applicant): Background. Animal data indicate that the widely used illicit drug ecstasy (mdma) and its more potent metabolite, mda (previously known as the "love drug"), can damage brain serotonin neurones. However, results of limited in vivo neuroimaging studies attempting to measure levels of brain serotonin markers in human drug users are uncertain because of problems in experimental design and in validity and reliability of the radiolabeled probes used to assess serotonin neurone integrity. Broad objective. Our broad objective is to establish the extent to which ecstasy and mda "harms" human brain. Specific Aim, Hypothesis, and Design. Our major SPECIFIC AIM is to establish by PET (positron emission tomography) neuroimaging whether levels of a key component of serotonin neurones, the serotonin transporter (SERT), as inferred from binding of our recently developed probe, [11C]-DASB, are reduced in brain of chronic users of ecstasy and in users of mda as compared with those in a matched control group. Our investigation includes the use of forensic hair analysis to prove unequivocally chronic use of ecstasy/mda, and utilisation of a new SERT radiolabeled probe, developed by our PET centre, which is free of the validity/reliability problems associated with previous radiotracers. Health relevance. The obtained data will provide useful information on the question of whether ecstasy and mda (a drug which we believe will increasingly become more popular) might compromise function of brain serotonin neurones in humans. More broadly, our data will help define the contribution of different neuroanatomical components of the brain serotonin system to human behavior.