In vivo mesolimbic D2/3 receptor binding predicts posttherapeutic clinical responses in restless legs syndrome: a positron emission tomography study

Although D2/3 agonists have been used as a first-line medication for idiopathic restless legs syndrome (iRLS), findings on D2/3 receptors have been inconsistent. Here, we aimed to clarify the contribution of D2/3 receptor function to the clinical symptoms of iRLS by comparing the binding potential (BPND) of [C-11]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naive, iRLS patients and eight age-matched healthy subjects were scanned with positron emission tomography (PET). After PET scans, all patients received pramipexole (0.125 mg) orally for 2 weeks. Patients were evaluated every day with several standardized clinical tests. The BPND values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [C-11] raclopride BPND in the mesolimbic dopamine region (nucleus accumbens (NA) and caudate) was significantly lower in the iRLS group. No significant differences between groups were observed in the putamen. The NA [C-11] raclopride BPND levels correlated negatively with clinical severity scores and positively with the degree of posttreatment improvement in iRLS. The present results suggest that alterations in mesolimbic D2/3 receptor function reflect the pathophysiology of iRLS, and the baseline availability of D2/3 receptors may predict the clinical outcome after D2/3 agonist treatment. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 654-662; doi:10.1038/jcbfm.2011.201; published online 11 January 2012