Increased synaptic dopamine in the putamen in restless legs syndrome

Sleep. 2013 Jan 1;36(1):51-7. doi: 10.5665/sleep.2300.

Abstract

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 [(11)C]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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / metabolism
  • Circadian Rhythm
  • Dopamine / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Putamen / metabolism*
  • Receptors, Dopamine D2 / metabolism
  • Restless Legs Syndrome / metabolism*
  • Synapses / metabolism*

Substances

  • Receptors, Dopamine D2
  • Dopamine