PET STUDIES OF MODAFINIL (PROVIGIL)

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。 本研究的目的是评估在临床规定剂量(口服200 mg或400 mg)下莫达非尼是否与多巴胺转运体结合，并评估它是否增加人脑中的DA。我们有以下具体目标： 具体目标1：我们将使用PET和[11C]可卡因(一种与多巴胺转运体(DAT)结合的放射性示踪剂)在10名正常受试者中确定莫达非尼(200 mg，口服)阻断DAT的程度。在同一组受试者中，我们将使用[11C]拉氯普利来确定200毫克莫达非尼是否会升高突触多巴胺，这是一种与多巴胺受体结合的放射性示踪剂，对突触多巴胺的变化很敏感。每个受试者将进行四次正电子发射计算机断层扫描，其中两次将以安慰剂为基线，两次将在服用莫达非尼2小时后进行。 具体目标2：在第二组10名受试者中，将确定莫达非尼(400 mg，口服)阻断DAT并提高突触多巴胺的程度。 假设：我们预测与安慰剂相比，莫达非尼以剂量依赖的方式阻断DAT并升高突触多巴胺。

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.