PET STUDIES OF MODAFINIL (PROVIGIL)

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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.