5-HT sub(2A)-mu opioid receptor mechanisms in the hypothalamus mediate interleukin-1 beta fever in rats

Direct administration of interleukin-1 beta (IL-1 beta ) 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-1 beta was significantly attenuated by pretreatment with intracerebroventricular injection of 5-HT sub(2A) receptor antagonists including cyproheptadine, ketanserin, or mianserin. In addition, the IL-1 beta -induced fever was mimicked by intracerebroventricular administration of a 5-HT sub(2A) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-amionpropane (DOI). The DOI-induced (present results) or IL-1 beta -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-NH sub(2)) or 5-HT receptor antagonists (e.g., ketanserin or cyproheptadine). These findings suggest that a 5-HT sub(2A)-mu opioid receptor mechanism in the hypothalamus may mediate the IL-1 beta fever.