Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin-1β-, and leptin-induced anorexia

We examined the role of serotonin (5-HT) and the 5-HT1A and 5-HT2c receptors in the anorectic effects of centrally administered lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and leptin. Food intake was measured in rats after intracerebroventricular (ICV) injections of LPS (20 ng), IL-1beta (10 ng), or leptin (1mug) at lights out, followed by intraperitoneal (IP) injections of either the 5-HT1A autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) (125 mug/kg) or the 5-HT2C receptor antagonist SB 242084 (0.3 mg/kg) at the onset of anorexia. SB 242084 significantly attenuated the food intake reduction caused by all compounds (all P<.01). IP 8-OH-DPAT attenuated ICV IL-1beta-induced anorexia (P<.01). We also tested the involvement of the median raphe 5-HT1A receptors in peripheral LPS-and IL-1beta-induced anorexia. Rats were injected intraperitoneally with either LPS (100 mug/kg) or IL-1beta (2 mug/kg) at lights out, and 8-0H-DPAT (4 nmol) was administered directly into the median raphe nucleus at the onset of anorexia. Median raphe injections of 8-OH-DPAT significantly attenuated both IL-1beta- and LPS-induced anorexia (both P<.01). These results implicate the 5-HT2C receptors in the mediation of central LPS-, IL-1beta-, and leptin-induced anorexia. Our results also suggest that the midbrain raphe nuclei play a role in mediating the anorectic response to peripheral LPS and IL-1beta. (C) 2003 Elsevier Science Inc. All rights reserved.