The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome

Research output: Contribution to journalArticle

Abstract

Study Objectives: 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 11C-methylphenidate and PET techniques. Design: 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. Participants: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)341-347
Number of pages7
JournalSleep
Volume34
Issue number3
StatePublished - Mar 1 2011

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Restless Legs Syndrome
Dopamine Plasma Membrane Transport Proteins
Single-Photon Emission-Computed Tomography
Corpus Striatum
Methylphenidate
Membranes
Putamen

Keywords

  • Dopamine transporter
  • Positron emission tomography
  • Restless leg syndrome
  • Striatum

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

Cite this

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title = "The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome",
abstract = "Study Objectives: 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 11C-methylphenidate and PET techniques. Design: 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. Participants: 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. Conclusion: 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.",
keywords = "Dopamine transporter, Positron emission tomography, Restless leg syndrome, Striatum",
author = "Earley, {Christopher J} and Hiroto Kuwabara and Wong, {Dean Foster} and Charlene Gamaldo and Rachel Salas and Brasic, {James R} and Ravert, {Hayden T.} and Dannals, {Robert F} and Richard Allen",
year = "2011",
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volume = "34",
pages = "341--347",
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T1 - The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome

AU - Earley, Christopher J

AU - Kuwabara, Hiroto

AU - Wong, Dean Foster

AU - Gamaldo, Charlene

AU - Salas, Rachel

AU - Brasic, James R

AU - Ravert, Hayden T.

AU - Dannals, Robert F

AU - Allen, Richard

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Study Objectives: 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 11C-methylphenidate and PET techniques. Design: 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. Participants: 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. Conclusion: 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.

AB - Study Objectives: 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 11C-methylphenidate and PET techniques. Design: 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. Participants: 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. Conclusion: 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.

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KW - Positron emission tomography

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