Brain Advance Access published online on July 1, 2006
Brain, doi:10.1093/brain/awl163
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1 Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
* To whom correspondence should be addressed. Clinical observations support a central role of the dopamine system in restless legs syndrome (RLS) but previous imaging studies of striatal dopamine D2-receptors have yielded inconclusive results. Extrastriatal dopaminergic function has hitherto not been investigated. Sixteen RLS patients naïve to dopaminergic drugs and sixteen matched control subjects were examined with PET. [11C]Raclopride and [11C]FLB 457 were used to estimate D2-receptor availability in striatum and extrastriatal regions, respectively. Examinations were performed both in the morning (starting between 10:00 and 12:00 h) and evening (starting at 18:00 h). Measures were taken to monitor and control for head movement during data acquisition. In the striatum, patients had significantly higher [11C]raclopride binding potential (BP) values than controls. In extrastriatal regions, [11C]FLB 457 BP was higher in patients than controls, and in the regional analysis the difference was statistically significant in subregions of thalamus and the anterior cingulate cortex. The diurnal variability in BP with [11C]FLB 457 and [11C]raclopride was within the previously reported test-retest reproducibility for both radioligands. The study supports involvement of the dopamine system in both striatal and extrastriatal brain regions in the pathophysiology of RLS. The brain regions where differences in D2-receptor binding were shown are implicated in the regulation of affective and motivational aspects of sensory processing, suggesting a possible pathway for sensory symptoms in RLS. Increased D2-receptor availability in RLS may correspond to higher receptor densities or lower levels of endogenous dopamine. Both interpretations are consistent with the hypothesis of hypoactive dopaminergic neurotransmission in RLS, as increased receptor levels can be owing to receptor upregulation in response to low levels of endogenous dopamine. The results do not support variations in dopamine D2-receptor availability as a correlate to the diurnal rhythm of RLS symptoms.
Received April 19, 2006
Revised May 10, 2006
Accepted May 22, 2006
Article
Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding
Simon 
ervenka 1 *,
Sven E. Pålhagen 2,
Robert A. Comley 3,
Georgios Panagiotidis 4,
Zsolt Cselényi 1,
Julian C. Matthews 5,
Robert Y. Lai 6,
Christer Halldin 1,
and
Lars Farde 1
2 Department of Neurology, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden
3 Translational Medicine and Genetics, GlaxoSmithKline, Cambridge, UK
4 Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden
5 Translational Medicine and Genetics, GlaxoSmithKline, Cambridge, UK; The University of Manchester, Wolfson Molecular Imaging Centre, Manchester, UK
6 Neurology Discovery Medicine, GlaxoSmithKline, Harlow, UK
Simon ervenka, E-mail: simon.cervenka{at}ki.se
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