Pharmacological, but not genetic, disruptions in 5-HT(2C) 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-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.
Asarian
Lori
L
Institute of Animal Science, ETH-Zürich, Schorentstr 16, 8603, Schwerzenbach, Switzerland. lasarian@ethz.ch
Kopf
Brigitte S
BS
Geary
Nori
N
Langhans
Wolfgang
W
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
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