title: 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ding
authors.forename: Alan
authors.initials: A
authors.lastname: Cowan
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002211:Capsaicin; D005473:Fluoxetine; D044348:Receptors, Serotonin, 5-HT2; D018689:Sensory System Agents; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors