PET STUDIES OF METHAMPHTAMINE NEUROTOXICITY IN HUMANS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在动物体内，甲基苯丙胺是一种有文献记载的多巴胺(DA)神经毒素。甲基苯丙胺对人类是否也有神经毒性尚不确定，这主要是因为很难评估活着的人脑中多巴胺神经元的完整性。正电子发射断层扫描(PET)与神经元特异性配体结合使用，是一种非侵入性成像技术，可用于研究活体人类的大脑DA神经元。例如，[11C]Win-35,428和/或[11C]DTBZ的PET成像最近促进了对轻度帕金森病患者DA神经元损伤的成功检测，这是一种以大脑DA神经元退化为特征的神经退行性疾病。本项目的总体目标是使用[11C]Win-35,428和[11C]DTBZ进行PET成像，并结合使用DA耗竭剂α-甲基对酪氨酸(Ampt)进行的药理学挑战研究，以确定先前暴露于高剂量甲基苯丙胺的人类是否显示出多巴胺能神经元损伤的证据。除了正电子发射计算机断层扫描和AMPT的药理学挑战外，所有受试者都将接受常规的医学、心理和实验室评估，包括详细的身体和神经检查，以及利用DSM-IV预定面试进行的结构化精神病学面试。该项目的长期目标是更好地描述娱乐性接触甲基苯丙胺的公共健康风险/后果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In animals, methamphetamine is a documented dopamine (DA) neurotoxin. Whether methamphetamine is also neurotoxic in humans has not been determined, largely because of the difficulty in assessing dopamine neuronal integrity in the living human brain. Positron emission tomography (PET), when used in conjunction with neuron specific ligands, is a non-invasive imaging technique that can be used to study brain DA neurons in living humans. For example, PET imaging with [11C]WIN-35,428 and/or [11C]DTBZ has recently facilitated the successful detection of DA neuron damage in patients with mild Parkinson's disease, a neurodegenerative condition characterized by degeneration of brain DA neurons. The overall goal of the present project is to use PET imaging with [11C]WIN-35,428 and [11C]DTBZ, in conjunction with pharmacologic challenge studies using the DA-depleting agent alpha-methyl-paratyrosine (AMPT), to ascertain whether humans previously exposed to high doses of methamphetamine show evidence of dopaminergic neuronal injury. In addition to the PET scans and pharmacological challenge with AMPT, all subjects will undergo routine medical, psychological, and laboratory evaluation, including a detailed physical and neurological examination, and a structured psychiatric interview using the Scheduled Interview for DSM-IV. The long-term goal of the project is to better delineate the public health risks/consequences of recreational methamphetamine exposure.