DOPAMINE - RESTLESS LEGS SYNDROME CONNECTIONS

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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 sensory-motor disorder in which the dopaminergic system and brain iron appear to play a role. The dramatic symptomatic response to L-DOPA in over 98% of RLS subjects and the induction of RLS-like symptoms with DA antagonists provide convincing evidence for the role of the dopaminergic (DAergic) system in the production of RLS symptoms. Autopsy, CSF, MRI, and IV iron treatment data indicate a role of brain-iron deficiency in RLS. This Proposal is designed to explore the differences in the DAergic systems in RLS patients, evaluate changes in circadian changes in the DAergic systems in RLS patients, define the relationship between changes in iron and changes in the DAergic system in RLS (i.e. reduced iron in the brain precipitates alterations in DAergic system) and determine if there is correlation between DAeric activity and RLS symptoms. The specific aims of the current Project are: Aim 1: To assess dopaminergic differences between RLS patients and controls by using PET studies of D2R binding. Aim 2: To evaluate the normal circadian changes in the dopaminergic systems and assess differences in these circadian changes between RLS and normal controls by comparing PET DAergic activity in patients and controls scanned 7:30p-11 pm and 8:30am-12:00pm. Aim 3: To determine if there are any significant correlation between the abnormalities in the CNS dopamine system and CNS iron status in RLS by correlation of PET studies of DAergic system and MRI measures of regional brain concentrations of iron. Aim 4: To determine if there is any significant correlation between measurements of DAergic activity and RLS symptoms (determined by daily symptom log and periodic leg movements per hour).