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Advances in Pharmacological Sciences
Volume 2012 (2012), Article ID 312041, 9 pages
http://dx.doi.org/10.1155/2012/312041
Research Article

Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice

1Department of Pharmacology, Drug Discovery and Preclinical Development, ESTEVE, Avenida Mare de Déu de Montserrat 221, 08041 Barcelona, Spain
2UMR 894 INSERM-CPN/UPMC, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France

Received 17 February 2012; Accepted 27 April 2012

Academic Editor: Karim A. Alkadhi

Copyright © 2012 Alex Brenchat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

No study has ever examined the effect of 5-HT7 receptor agonists on nociception by using 5-HT7 receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II of the formalin test did not differ in 5-HT7 receptor knockout mice and paired wild-type controls. Similarly, there was no significant difference in basal body temperature between both genotypes. Subcutaneous administration of 5-HT7 receptor agonists AS-19 (10 mg/kg), E-57431 (10 mg/kg), and E-55888 (20 mg/kg) significantly reduced formalin-induced licking/biting behavior during the phase II of the test in wild-type but not in 5-HT7 receptor knockout mice. At these active analgesic doses, none of the three 5-HT7 receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT7 receptor knockout mice. However, a significant decrease in body temperature was observed at a higher dose (20 mg/kg) of AS-19 and E-57431 in both genotypes. Our data strongly suggest that the 5-HT7 receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT7 receptors. These results also strengthen the idea that the 5-HT7 receptor plays a role in thermoregulation, but by acting in concert with other receptors.