title: Pharmacological, but not genetic, disruptions in 5-HT(2C) receptor function attenuate LPS anorexia in mice.
abstract: 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-HT(2C)R) attenuates LPS anorexia in rats. Here we used pharmacological and genetic approaches to examine the role of the 5-HT(2C)R in LPS anorexia in mice. In Experiment 1, SB 242084, a potent and selective 5-HT(2C) antagonist (0.3 mg/kg) was injected intraperitoneally 15 min before intraperitoneal LPS (2 microg/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 microg/kg) injections in mice with a genetic deletion of 5-HT(2C)R 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-HT(2C)R. Our genetic data, in contrast, suggest that 5-HT(2C)R is not a necessary part of LPS anorexia.
authors.affiliation: Institute of Animal Science, ETH-Zürich, Schorentstr 16, 8603, Schwerzenbach, Switzerland. lasarian@ethz.ch
authors.forename: Lori
authors.initials: L
authors.lastname: Asarian
authors.forename: Brigitte S
authors.initials: BS
authors.lastname: Kopf
authors.forename: Nori
authors.initials: N
authors.lastname: Geary
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D020296:Animals, Congenic; D000855:Anorexia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000172:deficiency / Q000235:genetics; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D017931:DNA Primers; D007211:Indoles; D008070:Lipopolysaccharides; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists