Distribution, Level, Pharmacology, Regulation, and Signaling of 5-HT6 Receptors in Rats and Marmosets With Special Reference to an Experimental Model of Parkinsonism
2011 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 519, no 9, 1815-1827 p.Article in journal (Refereed) Published
Serotonin 5-HT6 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-HT6 receptor antagonist [I-125]SB-258585 was similar in marmosets and rats. In both species, [I-125]SB-258585 binding was enriched in the caudate-putamen. Various recently developed agonists and antagonists toward 5-HT6 receptors exhibited similarities in their abilities to displace [I-125]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 [I-125]SB-258585 binding in the caudate-putamen of both marmosets and rats. Nonetheless, acute administration of the 5-HT6 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-HT6 receptors following dopamine depletion. In conclusion, this study provides evidence for significant similarities in the distribution, level, pharmacology, and regulation of 5-HT6 receptors between rats and marmosets.
Place, publisher, year, edition, pages
2011. Vol. 519, no 9, 1815-1827 p.
serotonin, GPCR, 6-hydroxydopamine, EMDT, SB-258585, caudate-putamen
IdentifiersURN: urn:nbn:se:uu:diva-154293DOI: 10.1002/cne.22605ISI: 000290527500012PubMedID: 21452237OAI: oai:DiVA.org:uu-154293DiVA: diva2:419920