NEUROIMAGING MDMA NEUROTOXICITY: DOPAMINE STUDIES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。(V)3,4-亚甲基二氧甲基苯丙胺（MDMA，摇头丸）是一种流行的娱乐性药物，在实验动物中是一种强效的脑血清素（5-HT）神经毒素。越来越多的证据表明，MDMA也会对人类大脑产生5-羟色胺神经毒性作用。普遍的观点是MDMA是一种选择性的5-HT神经毒素，因为在动物中，多巴胺（DA）和去甲肾上腺素神经元通常不受影响。然而，最近我们发现，使用与娱乐性MDMA使用者经常使用的MDMA剂量方案非常相似的MDMA剂量方案治疗的猴子和狒狒除了显著的5-HT神经毒性外，还会产生深刻的DA神经毒性。这一意想不到的发现提出了一种可能性，即除了5-HT神经损伤外，一些MDMA使用者可能会遭受严重的DA神经损伤。这项提议的研究是一个更大的研究项目的一部分，该项目旨在评估MDMA对人体的神经毒性。本研究的具体目的是确定先前在几个小时内服用多剂量MDMA的个体（“暴食者”）是否会出现DA和水泡单胺转运蛋白（dat和VMATs）的显著减少，类似于最近在非人灵长类动物中发现的情况。

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. (V)3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy), a popular recreational drug, is a potent brain serotonin (5-HT) neurotoxin in experimental animals. There is mounting evidence that MDMA also produces brain 5-HT neurotoxic effects in humans. The prevailing view has been that MDMA is a selective 5-HT neurotoxin, since in animals, dopamine (DA) and norepinephrine neurons are typically unaffected. However, recently we have found that monkeys and baboons treated with a dosage regimen of MDMA modeled closely after one often used by recreational MDMA users develop profound DA neurotoxicity, in addition to significant 5-HT neurotoxicity. This unexpected finding raises the possibility that, in addition to 5-HT neural injury, some MDMA users may sustain significant DA neural injury. The proposed study is part of a larger research project designed to assess the neurotoxic potential of MDMA in humans. The specific aim of this study is to determine if individuals who have previously taken multiple doses of MDMA over several hours ("bingers") develop profound reductions in DA and vesicular monoamine transporters (DATs and VMATs) similar to those recently discovered in nonhuman primates.