A role for serotonin in lipopolysaccharide-induced anorexia in rats

Rats consistently reduce their food intake following injection of bacterial lipopolysaccharides (LPS). Because LPS increases CNS serotonin (5-HT) turn over, and because increases in CNS 5-HT turnover are associated with a decr ease in food intake, we conducted a series of studies to examine 5-HT's pot ential role in LPS-induced anorexia. Chronic CNS 5-HT depletion by cisterna magna (CM) administration of 5,7-dihydroxytryptamine (5,7-DHT) failed to a ttenuate LPS-induced (100 mug/kg, ip) anorexia. In subsequent experiments, LPS was injected at lights out (hour 0) and [8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT)] or N-CBZ-[(8 beta )1,6-dimethylergolin-8-yl]methylam ine (metergoline) was injected at hour 5- the time when LPS-treated rats be come anorectic. Food intake was measured during the subsequent 2 h. In LPS- treated rats, 8-OH-DPAT (62.5, 125, or 250 mug/kg, sc) injection increased food intake. In a 2 x 2 factorial arrangement of LPS and 8-OH-DPAT, 125 mug /kg 8-OH-DPAT increased food intake significantly more in LPS-treated rats than in non-LPS-treated rats (significant LPS x 8-OH-DPAT interaction). In LPS-treated rats, 1 and 5 mg/kg metergoline significantly enhanced food int ake. However, in a 2 x 2 arrangement of LPS and metergoline, 1 mg/kg meterg oline failed to increase food intake in LPS and non-LPS-treated rats in two separate trials. The ability of the 5-HT1A receptor agonist 8-OH-DPAT to a ttenuate LPS-induced anorexia in rats supports a role of 5-HT in LPS-induce d anorexia. (C) 2001 Elsevier Science Inc. All rights reserved.