Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin-1 beta-, and leptin-induced anorexia.
We examined the role of serotonin (5-HT) and the 5-HT(1A) and 5-HT(2C) receptors in the anorectic effects of centrally administered lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), and leptin. Food intake was measured in rats after intracerebroventricular (ICV) injections of LPS (20 ng), IL-1 beta (10 ng), or leptin (1 microg) at lights out, followed by intraperitoneal (IP) injections of either the 5-HT(1A) autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) (125 microg/kg) or the 5-HT(2C) 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-1 beta-induced anorexia (P<.01). We also tested the involvement of the median raphe 5-HT(1A) receptors in peripheral LPS- and IL-1 beta-induced anorexia. Rats were injected intraperitoneally with either LPS (100 microg/kg) or IL-1 beta (2 microg/kg) at lights out, and 8-OH-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-1 beta- and LPS-induced anorexia (both P<.01). These results implicate the 5-HT(2C) receptors in the mediation of central LPS-, IL-1 beta-, 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-1 beta.
von Meyenburg
Claudia
C
Department of Physiology and Animal Husbandry, Institute of Animal Sciences, Swiss Federal Institute of Technology, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland. claudia.vonmeyenburg@inw.agrl.ethz.ch
Langhans
Wolfgang
W
Hrupka
Brian J
BJ
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000503:physiopathology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000633:toxicity*; D020738:Leptin / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D007375:Interleukin-1; D020738:Leptin; D008070:Lipopolysaccharides; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists