title: PET studies of D2-receptor binding in striatal and extrastriatal brain regions: Biochemical support in vivo for separate dopaminergic systems in humans.
abstract: Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [11C]raclopride and [11C]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.
authors.affiliation: Department of Clinical Neuroscience, Stockholm Brain Institute/Karolinska Institute, Stockholm, Sweden. simon.cervenka@ki.se
authors.forename: Simon
authors.initials: S
authors.lastname: Cervenka
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
authors.forename: Erik
authors.initials: E
authors.lastname: Fransén
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
mesh_terms: D000368:Aged; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism
chemical_list: D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride; D004298:Dopamine