PET STUDIES OF HUMANS EXPOSED TO MDMA (ECSTASY)

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。在动物身上，娱乐药物3，4-亚甲基二氧基甲基苯丙胺(MDMA)是一种有文献记载的5-羟色胺(5-HT)神经毒素。MDMA对人类是否也有神经毒性尚不清楚，但最近有证据表明，MDMA使用者的脑脊液(CSF)中5-羟色胺代谢产物5-HIAA的浓度低于对照组。评估MDMA对人类的神经毒性潜力的困难很大程度上源于这样一个事实，即没有直接的方法来研究活着的人脑中的神经元。正电子发射断层扫描(PET)与5-羟色胺神经元的放射性配基结合使用时，是一种可以用来研究人类5-羟色胺神经元在生命过程中状态的成像技术。事实上，初步观察表明，带有5-羟色胺转运体配体[11C]MCN-5652和[11C]DASB的正电子发射计算机断层扫描(PET)成像对于检测MDMA损伤的狒狒脑内5-羟色胺的缺陷是有用的。该项目的总体目标是确认这一发现，并将其推广到人类身上。此外，在这项协议中，有一项试点研究，在MDMA用户和匹配的对照组中使用fMRI方法来测量延迟匹配到样本任务执行期间的脑血流激活。该项目的长期目标是：1)进一步验证[11C]MCN-5652和[11C]DASB用于用PET研究活体人脑中5-羟色胺神经元的有效性；以及2)更好地确定MDMA对人类的神经毒性潜力。

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, the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is a documented serotonin (5-HT) neurotoxin. Whether or not MDMA us also neurotoxic in humans is not known, but there is recent evidence that it is, i.e., human MDMA users have lower concentrations of the 5-HT metabolite 5-HIAA in their cerebrospinal fluid (CSF) than controls. The difficulty in assessing the neurotoxic potential of MDMA in humans stems largely from the fact that there are not direct methods for investigating neurons in the living human brain. Positron emission tomography (PET), when used in conjunction with a radioligand specific for the 5-HT neuron, is an imaging technique that could be used to study that status of 5-HT neurons in humans druing life. Indeed, preliminary observations suggest that PET imaging with 5-HT transporter ligands, [11C]McN-5652 and [11C]DASB, are useful for detecting brain 5-HT deficits in MDMA lesioned baboons. The overall goal of the project is to confirm this finding and extend it to humans. Also, there is a pilot study in this protocol using fMRI methods in MDMA users and matched controls to measure cerebral blood flow activation during performance of a delayed matching to sample task. The long-term goals of this project are: 1) to further validate the usefulness of [11C]McN-5652 and [11C]DASB for studying 5-HT neurons in the living human brain with PET; and 2) to better define the neurotoxic potential of MDMA in humans.