title: The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome.
abstract: OBJECTIVE
  Prior studies, all using SPECT techniques, failed to find any differences for dopamine transporter (DAT) in restless legs syndrome (RLS) subjects. The distinct pharmacokinetic properties associated with SPECT-determined DAT along with rapid biodynamic changes in DAT may, however, have missed membrane-bound DAT differences. The current studies assessed real-time DAT binding potentials (BP) in striatum of RLS patients using (11)C-methylphenidate and PET techniques.
  
  
  METHODS
  RLS medications were stopped at least 11 days prior to the PET study. Clinical severity of RLS was also assessed. PET scans were performed at 2 different times of day (starting at 08:30 and 19:30) in separate groups of subjects. The primary outcome measure was total striatal DAT BP.
  
  
  METHODS
  Thirty-six patients with primary RLS and 34 age- and gender-matched controls.
  
  
  RESULTS
  RLS subjects had significantly lower DAT binding in the striatum compared to controls on both the Day and the Night scans. DAT was decreased in putamen and caudate but not the ventral striatum of RLS subjects. There were no diurnal differences in DAT for the total group or for control and RLS separately. DAT BP did not correlate with any clinical measures of RLS.
  
  
  CONCLUSIONS
  The current study found a significant decrease in DAT BP in two independent studies. These results when viewed along with prior RLS SPECT and autopsy studies of DAT, and cell culture studies with iron deficiency and DAT, suggest that membrane-bound striatal DAT, but not total cellular DAT, may be decreased in RLS.
authors.affiliation: Department of Neurology, Division of Nuclear Medicine, Johns Hopkins University, Baltimore, MD, USA. cearley@jhmi.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Earley
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kuwabara
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Charlene
authors.initials: C
authors.lastname: Gamaldo
authors.forename: Rachel
authors.initials: R
authors.lastname: Salas
authors.forename: James
authors.initials: J
authors.lastname: Brasic
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000737:chemistry* / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D049268:Positron-Emission Tomography; D012148:Restless Legs Syndrome / Q000378:metabolism*; D012890:Sleep / Q000502:physiology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins