Increased synaptic dopamine in the putamen in restless legs syndrome

Study Objectives: Prior studies using positron emission tomography (PET) or single-photon emission computed tomography techniques have reported inconsistent findings regarding differences between patients with restless legs syndrome (RLS) and control patients in the striatal dopamine-2 receptor (D2R) binding potentials (BP). D2R-BP does reflect receptor-ligand interactions such as receptor affinity (K_d) and density (β_max) or neurotransmitter synaptic concentrations. Thus, differences in D2R-BP reflect changes in these primary factors. PET techniques are currently available to estimate D2R β_max and K_d. Design: Separate morning and evening PET scans were performed. The D2R-BP were measured in basal ganglia using [¹¹C]raclopride. Setting: Academic medical center. Patients or Participants: Thirty-one patients with primary RLS and 36 age- and sex-matched control patients completed the study. Measures and Results: Patients with RLS had lower D2R-BP in putamen and caudate but not the ventral striatum. A subgroups analysis of those RLS patients who had not previously taken dopaminergic medications continued to show a significantly lower D2R-BP in the posterior putamen. D2R-BP did not differ between night and day for either group. D2R β_max and K_d did not differ significantly between patients with RLS and control patients but did show a strong and significant increase at night in the ventral striatum. Primary and secondary clinical measures of disease status failed to show any relation to D2R in any brain region. Conclusions: Given the lack of any difference in either β_max or K_d and the prior studies supporting an increase in presynaptic dopaminergic activity, the current changes found in D2R-BP likely reflect an increase in synaptic dopamine.