Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice. (19th June 2012)

• Record Type: Journal Article
• Authors: Brenchat, Alex; Rocasalbas, Maria; Zamanillo, Daniel; Hamon, Michel; Vela, José Miguel; Romero, Luz
• Other Names: Alkadhi Karim A. Academic Editor.
• Is Part Of: Advances in pharmacological sciences. Volume 2012(2012)
• Publication Date: 2012-06-19
• Subjects: Pharmacology -- Periodicals; Pharmacological Phenomena; Pharmacology; Periodicals; 615.1
• DOI: 10.1155/2012/312041
• Languages: English
• ISSNs: 1687-6334

Abstract

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.