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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Assessment of 5-HT(7) Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus
Alex Brenchat1, Maria Rocasalbas, Daniel Zamanillo
1Department of Pharmacology, Drug Discovery and Preclinical Development, ESTEVE, Avenida Mare de Déu de Montserrat 221, 08041 Barcelona, Spain.
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.
