INCREASED SYNAPTIC DOPAMINE IN THE PUTAMEN IN RESTLESS LEGS SYNDROME
Increased Synaptic Dopamine in the Putamen in Restless Legs Syndrome
Christopher J. Earley, MB, BCh, PhD1; Hiroto Kuwabara, PhD2; Dean F. Wong, MD, PhD2,3,4; Charlene Gamaldo, MD1; Rachel E. Salas, MD1; James R. Brašić, MD, MPH2; Hayden T. Ravert, PhD2; Robert F. Dannals, PhD2; Richard P. Allen, PhD1
1Departments of Neurology; 2Radiology, Division of Nuclear Medicine; 3Psychiatry; 4Neuroscience, Johns Hopkins University, Baltimore, MD
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 (Kd) and density (βmax) or neurotransmitter synaptic concentrations. Thus, differences in D2R-BP reflect changes in these primary factors. PET techniques are currently available to estimate D2R βmax and Kd.
Separate morning and evening PET scans were performed. The D2R-BP were measured in basal ganglia using [11C]raclopride.
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 βmax and Kd 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.
Given the lack of any difference in either βmax or Kd 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.
Earley CJ; Kuwabara H; Wong DF; Gamaldo C; Salas RE; Brašić JR; Ravert HT; Dannals RF; Allen RP. Increased synaptic dopamine in the putamen in restless legs syndrome. SLEEP 2013;36(1):51–57.