Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor

Rats consistently reduce their food intake following injections of bacterial lipopolysaccharides (LPS). Because inhibition of serotonergic (5-HT) activity by 8-OH-DPAT (5-HT1A activation) attenuates LPS-induced anorexia, we conducted a series of studies to examine whether other 5-HT-receptors are involved in the mediation of peripheral LPS-induced anorexia. In all experiments, rats were injected with LPS (100 mug/kg body weight [BW] ip) at lights out (hour 0). Antagonists were administered peripherally at hour 4, shortly after the onset of anorexia, which presumably follows the enhanced cytokine production after LPS. Food intake was then recorded during the subsequent 2 h or longer. 5-HT receptor antagonists cyanopindolol and SB 224289 (5-HT1B), ketanserin (5-HT2A), RS-102221 (5-HT2C, and metoclopramide (5-HT3) failed to attenuate LPS-induced anorexia. In contrast, both ritanserin (5-HT2A/C-receptor antagonist) (0.5 mg/kg BW) and SB 242084 (5-HT2C) (0.3 mg/kg BW) attenuated LPS-induced anorexia at doses that did not alter food intake in non-LPS-treated rats (all P<.01). Our results suggest that at least part of the anorexia following peripheral LPS administration is mediated through an enhanced 5-HT-ergic activity and the 5-HT2C receptor. (C) 2002 Elsevier Science Inc. All rights reserved.