DOPAMINE AND IRON IN RESTLESS LEG SYNDROME

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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. Restless legs syndrome (RLS) is a common sleep disorder that is reported to effect beween 2 and 5% of the population. Although the pathophysiology of RLS is unknown, there is a significant body of preclinical and clinical research that strongly implicates the brain DA system, and some evidence that brain iron deficiency may also play a role. The proposed research will use positron emission tomographic (PET) methods with radioligands selective for the dopamine 2 receptor (D2R) and the dopamine transporter (DAT), pre- and post- pharmacological challenge with d-amphetamine, to assess the status of the brain dopamine systems in patients with RLS compared to matched controls. In addition, magnetic resonance spectroscopic (MRS) methods, along with cerebrospinal measures of ferritin will be used to measure CNS iron, and serial plasma measures of prolactin will be used as an indirect measure of tuberoinfundibular DA activity. The overarching goals of the project are to better characterize dopaminergic dysfunction in patients with RLS, and its relationship to CNS iron content.