Pharmacological, but not genetic, disruptions in 5-HT2C receptor function attenuate LPS anorexia in mice

Peripheral administration of bacterial lipopolysaccharide (LPS) elicits anorexia in several species, including rats and mice. There is strong evidence that antagonism of serotonergic activity at 2C receptors (5-HT2CR) attenuates LPS anorexia in rats. Here we used pharmacological and genetic approaches to examine the role of the 5-HT2CR in LPS anorexia in mice. In Experiment 1, SB 242084, a potent and selective 5-HT2C antagonist (0.3 mg/kg) was injected intraperitoneally 15 min before intraperitoneal LPS (2 μg/kg) injections just prior to dark onset in c57BL/6 mice. Food intake was recorded 1, 2 and 4 h after LPS administration. In Experiment 2, we recorded 2, 4 and 24 h food intake following dark onset intraperitoneal LPS (0.125, 0.25, 0.5, 1 and 2 μg/kg) injections in mice with a genetic deletion of 5-HT2CR and their WT controls. Our pharmacological results suggest that at least part of the anorexia following peripheral LPS administration is mediated by an increase in 5-HT-ergic activity at the 5-HT2CR. Our genetic data, in contrast, suggest that 5-HT2CR is not a necessary part of LPS anorexia.