title: Distribution, level, pharmacology, regulation, and signaling of 5-HT6 receptors in rats and marmosets with special reference to an experimental model of parkinsonism.
abstract: Serotonin 5-HT(6) receptors have been implicated in the regulation of cognition, locomotion, and mood, but the elucidation of their functions is complicated by conflicting data using various animal models. Here, a systematic evaluation showed that autoradiographic binding with the selective 5-HT(6) receptor antagonist [(125) I]SB-258585 was similar in marmosets and rats. In both species, [(125) I]SB-258585 binding was enriched in the caudate-putamen. Various recently developed agonists and antagonists toward 5-HT(6) receptors exhibited similarities in their abilities to displace [(125) I]SB-258585 binding in marmosets and rats. The rank order of pEC50 values were as follows: (+)EMDT-CR = EMD386088>MS-245 = 5-HT>EMDT>>(-)EMDT-CR; and (+)EMDT-CR = EMD386088>5-HT = MS-245 = EMDT>>(-)EMDT-CR, in marmosets and rats, respectively. Unilateral 6-hydroxydopamine lesioning of dopaminergic axons caused a significant decrease of [(125) I]SB-258585 binding in the caudate-putamen of both marmosets and rats. Nonetheless, acute administration of the 5-HT(6) receptor agonist EMDT to unilaterally 6-hydroxydopamine-lesioned rats, caused an induction of egr-1, homer, and enkephalin mRNAs in the dopamine-depleted hemisphere, indicating a supersensitization of 5-HT(6) receptors following dopamine depletion. In conclusion, this study provides evidence for significant similarities in the distribution, level, pharmacology, and regulation of 5-HT(6) receptors between rats and marmosets.
authors: Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden.
authors: Xiaoqun
authors: X
authors: Zhang
authors: Per E
authors: PE
authors: Andren
authors: Richard A
authors: RA
authors: Glennon
authors: Per
authors: P
authors: Svenningsson
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002144:Callithrix; D004195:Disease Models, Animal; D008297:Male; D020734:Parkinsonian Disorders / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor