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Distribution, Level, Pharmacology, Regulation, and Signaling of 5-HT6 Receptors in Rats and Marmosets With Special Reference to an Experimental Model of Parkinsonism
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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
Abstract [en]

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.
Keyword [en]
serotonin, GPCR, 6-hydroxydopamine, EMDT, SB-258585, caudate-putamen
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-154293DOI: 10.1002/cne.22605ISI: 000290527500012PubMedID: 21452237OAI: oai:DiVA.org:uu-154293DiVA: diva2:419920
Available from: 2011-05-30 Created: 2011-05-30 Last updated: 2011-11-18Bibliographically approved

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