NEUROIMAGING MDMA NEUROTOXICITY: DOPAMINE STUDIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 (V)3，4-亚甲基二氧基甲基苯丙胺(MDMA，摇头丸)是一种在实验动物中有效的脑5-羟色胺(5-HT)神经毒素，是一种流行的娱乐药物。越来越多的证据表明，MDMA也会对人类的大脑产生5-羟色胺的神经毒性作用。流行的观点认为MDMA是一种选择性的5-羟色胺神经毒素，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，用MDMA剂量方案治疗的猴子和狒狒，除了显著的5-羟色胺神经毒性外，还会出现严重的DA神经毒性，这种剂量方案与娱乐MDMA使用者经常使用的MDMA方案非常相似。这一意想不到的发现提出了一种可能性，即除了5-羟色胺神经损伤外，一些MDMA使用者可能遭受严重的DA神经损伤。这项拟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对人类的神经毒性潜力。这项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(“暴饮者”)是否像最近在非人类灵长类动物中发现的那样，在DA和囊泡单胺转运体(DAT和VMATs)方面发生显著减少。

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.