PET STUDIES OF METHAMPHTAMINE NEUROTOXICITY IN HUMANS

甲基苯丙胺对人类神经毒性的 PET 研究

• 批准号: 7375794
• 负责人: GEORGE A RICAURTE
• 金额: $ 0.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375794
• 关键词: PET; STUDIES; METHAMPHTAMINE; NEUROTOXICITY; HUMANS

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在动物中，甲基苯丙胺是一种记录在案的多巴胺（DA）神经毒素。甲基苯丙胺是否对人类也有神经毒性尚未确定，主要是因为难以评估活体人脑中多巴胺神经元的完整性。正电子发射断层扫描（PET），当与神经元特异性配体结合使用时，是一种非侵入性成像技术，可用于研究活体人类大脑DA神经元。例如，用[11 C]WIN-35，428和/或[11 C]DTBZ进行的PET成像最近促进了轻度帕金森病患者中DA神经元损伤的成功检测，帕金森病是一种以脑DA神经元变性为特征的神经变性病症。本项目的总体目标是使用[11 C]WIN-35，428和[11 C]DTBZ的PET成像，结合使用DA消耗剂α-甲基-对酪氨酸（AMPT）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是否显示多巴胺能神经元损伤的证据。 除了PET扫描和AMPT药理学激发外，所有受试者还将接受常规医学、心理和实验室评价，包括详细的体格和神经系统检查，以及使用DSM-IV计划访谈进行的结构化精神病学访谈。 该项目的长期目标是更好地描述娱乐性甲基苯丙胺接触的公共健康风险/后果。