PET STUDIES OF MODAFINIL (PROVIGIL)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是评估临床处方剂量（200 mg或400 mg，口服）莫达非尼是否与多巴胺转运蛋白结合，并评估其是否增加人脑中的DA。 我们有以下具体目标： 具体目标1：我们将使用PET和[11 C]可卡因（一种与10名正常受试者的多巴胺转运蛋白（DAT）结合的放射性示踪剂）确定莫达非尼（200 mg，口服）阻断DAT的程度。 在同一组受试者中，我们将使用[11 C]雷氯必利（一种与多巴胺受体结合并对突触多巴胺变化敏感的放射性示踪剂）确定200 mg莫达非尼是否升高突触多巴胺。 每例受试者将进行四次PET扫描，其中两次将在安慰剂组基线时进行，另两次将在莫达非尼给药后2小时进行。 具体目标二：在第二组10名受试者中，将确定莫达非尼（400 mg，口服）阻断DAT和升高突触多巴胺的程度。 假设：我们预测莫达非尼阻断DAT，并以剂量依赖性方式升高突触多巴胺。

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. The purpose of the current study is to assess if at the clinical prescribed doses (200 mg or 400 mg, oral) modafinil binds to the dopamine transporters and to assess if it increases DA in the human brain. We have the following specific aims: Specific Aim 1: We will determine the degree to which modafinil (200 mg, given orally) blocks the DAT using PET and [11C]cocaine, a radiotracer which binds to the dopamine transporter (DAT) in 10 normal subjects. In this same group of subjects we will determine whether 200 mg of modafinil elevates synaptic dopamine using [11C]raclopride, a radiotracer which binds to the dopamine receptor and is sensitive to changes in synaptic dopamine. There will be four PET scans in each subject, two of which will be baseline with placebo and two of which will be performed 2 hour after modafinil administration. Specific Aim 2: In a second group of 10 subjects, will determine the degree to which modafinil (400 mg, given orally) blocks the DAT and elevates synaptic dopamine. Hypotheses: We predict that modafinil blocks the DAT and elevates synaptic dopamine in a dose-dependent manner relative to placebo.