5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats

Numerous studies support a role for the endogenous 5-hydroxytryptamine (5-HT) system in the hypothermic effect of capsaicin. None of those studies, however, selectively delineate a role for 5-HT reuptake or 5-HT receptors in this regard. In the present investigation, we determined if the blockade of 5-HT reuptake or the activation of 5-HT1A or 5-HT2 receptors modulates capsaicin-evoked hypothermia. The administration of capsaicin (0.2–1 mg/kg, i.m.) produced dose-related hypothermia. Fluoxetine (10 mg/kg, i.p.), a selective serotonin reuptake inhibitor (SSRI), did not affect body temperature. For combined administration, pretreatment with fluoxetine (10 mg/kg, i.p.) significantly attenuated the hypothermia caused by capsaicin (0.5 and 1 mg/kg, i.m.). For the 5-HT receptor experiments, we pretreated rats with either WAY 100635, a 5-HT1A receptor antagonist, or mianserin, a 5-HT2 receptor antagonist, and then administered a fixed, hypothermic dose of capsaicin (1 mg/kg, i.m.). WAY 100635 (1 mg/kg, s.c.) administration did not affect capsaicin-evoked hypothermia. This indicates that 5-HT1A receptor activation does not play a major role in the hypothermic effect of capsaicin. In contrast, pretreatment with mianserin (10 mg/kg, i.p.) enhanced the hypothermic effect of capsaicin (1 mg/kg, i.m.). The present data reveal that capsaicin-evoked hypothermia in rats is attenuated by the blockade of 5-HT reuptake and enhanced by the antagonism of 5-HT2 receptors.