1. 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats.
- Author
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Ding Z, Cowan A, and Rawls SM
- Subjects
- Animals, Body Temperature drug effects, Brain drug effects, Brain physiopathology, Capsaicin pharmacology, Dose-Response Relationship, Drug, Drug Interactions physiology, Drug Synergism, Fluoxetine pharmacology, Hypothermia chemically induced, Hypothermia physiopathology, Male, Rats, Rats, Sprague-Dawley, Sensory System Agents pharmacology, Serotonin Antagonists pharmacology, Selective Serotonin Reuptake Inhibitors pharmacology, Synaptic Transmission drug effects, Synaptic Transmission physiology, Body Temperature physiology, Brain metabolism, Hypothermia metabolism, Receptors, Serotonin, 5-HT2 metabolism, Serotonin metabolism
- Abstract
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-HT(1A) or 5-HT(2) receptors modulates capsaicin-evoked hypothermia. The administration of capsaicin (0.2-1mg/kg, i.m.) produced dose-related hypothermia. Fluoxetine (10mg/kg, i.p.), a selective serotonin reuptake inhibitor (SSRI), did not affect body temperature. For combined administration, pretreatment with fluoxetine (10mg/kg, i.p.) significantly attenuated the hypothermia caused by capsaicin (0.5 and 1mg/kg, i.m.). For the 5-HT receptor experiments, we pretreated rats with either WAY 100635, a 5-HT(1A) receptor antagonist, or mianserin, a 5-HT(2) receptor antagonist, and then administered a fixed, hypothermic dose of capsaicin (1mg/kg, i.m.). WAY 100635 (1mg/kg, s.c.) administration did not affect capsaicin-evoked hypothermia. This indicates that 5-HT(1A) receptor activation does not play a major role in the hypothermic effect of capsaicin. In contrast, pretreatment with mianserin (10mg/kg, i.p.) enhanced the hypothermic effect of capsaicin (1mg/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-HT(2) receptors.
- Published
- 2008
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