5-HT2A-mu opioid receptor mechanisms in the hypothalamus mediate interleukin-1beta fever in rats.
Direct administration of interleukin-1beta (IL-1beta) into the lateral cerebral ventricle of rat brain, in addition to inducing febrile responses, upregulated the immunoreactivity of tryptophan hydroxylase in the preoptic anterior hypothalamus. The fever induced by IL-1beta was significantly attenuated by pretreatment with intracerebroventricular injection of 5-HT2A receptor antagonists including cyproheptadine, ketanserin, or mianserin. In addition, the IL-1beta-induced fever was mimicked by intracerebroventricular administration of a 5-HT2A receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-amionpropane (DOI). The DOI-induced (present results) or IL-1beta-induced (previous results) fever was further attenuated by pretreatment with an intracerebroventricular dose of mu-opioid receptor antagonists (e.g., buprenorphine or cyclic d-phe-cys-Try-d-Arg-Thr-pen-Thr-NH2) or 5-HT receptor antagonists (e.g., ketanserin or cyproheptadine). These findings suggest that a 5-HT2A-mu opioid receptor mechanism in the hypothalamus may mediate the IL-1beta fever.
Chio
Chung-Ching
CC
Department of Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan.
Tsai
Shu-Ming
SM
Wang
Jhi-Joung
JJ
Lin
Mao-Tsun
MT
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced* / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists
D007375:Interleukin-1; D044402:Receptor, Serotonin, 5-HT2A; D017450:Receptors, Opioid, mu; D058830:Serotonin 5-HT2 Receptor Antagonists