title: Assessment of 5-HT(7) Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice.
abstract: No study has ever examined the effect of 5-HT(7) receptor agonists on nociception by using 5-HT(7) 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-HT(7) 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-HT(7) 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-HT(7) receptor knockout mice. At these active analgesic doses, none of the three 5-HT(7) receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT(7) 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-HT(7) receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT(7) receptors. These results also strengthen the idea that the 5-HT(7) receptor plays a role in thermoregulation, but by acting in concert with other receptors.
authors: Department of Pharmacology, Drug Discovery and Preclinical Development, ESTEVE, Avenida Mare de Déu de Montserrat 221, 08041 Barcelona, Spain.
authors: Alex
authors: A
authors: Brenchat
authors: Maria
authors: M
authors: Rocasalbas
authors: Daniel
authors: D
authors: Zamanillo
authors: Michel
authors: M
authors: Hamon
authors: José Miguel
authors: JM
authors: Vela
authors: Luz
authors: L
authors: Romero