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VOLUME 36, ISSUE 01

INCREASED SYNAPTIC DOPAMINE IN THE PUTAMEN IN RESTLESS LEGS SYNDROME
Increased Synaptic Dopamine in the Putamen in Restless Legs Syndrome

http://dx.doi.org/10.5665/sleep.2300

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



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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 (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.

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 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.

Conclusions:

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.

Citation:

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.

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