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Distribution, level, pharmacology, regulation, and signaling of 5‐HT 6 receptors in rats and marmosets with special reference to an experimental model of parkinsonism
Author(s) -
Zhang Xiaoqun,
Andren Per E.,
Glen Richard A.,
Svenningsson Per
Publication year - 2011
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22605
Subject(s) - receptor , serotonin , biology , 5 ht receptor , dopaminergic , medicine , dopamine , endocrinology , pharmacology , agonist , dopamine receptor , raclopride , neuroscience , biochemistry
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. J. Comp. Neurol. 519:1815–1827, 2011. © 2011 Wiley‐Liss, Inc.