title: In vivo mesolimbic D2/3 receptor binding predicts posttherapeutic clinical responses in restless legs syndrome: a positron emission tomography study.
abstract: 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 (BP(ND)) of [(11)C]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naïve, 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 BP(ND) values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [(11)C]raclopride BP(ND) 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 [(11)C]raclopride BP(ND) 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.
authors.affiliation: Department of Biofunctional Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Oboshi
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kono
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Nakai
authors.forename: Etsuji
authors.initials: E
authors.lastname: Yoshikawa
authors.forename: Masami
authors.initials: M
authors.lastname: Futatsubashi
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Terada
authors.forename: Kang
authors.initials: K
authors.lastname: Kim
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D052160:Benzothiazoles / Q000008:administration & dosage*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D000077487:Pramipexole; D020891:Raclopride / Q000008:administration & dosage*; D011859:Radiography; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D012148:Restless Legs Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D000077487:Pramipexole