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) turnover, and because increases in CNS 5-HT turnover are associated with a decrease in food intake, we conducted a series of studies to examine 5-HT's potential role in LPS-induced anorexia. Chronic CNS 5-HT depletion by cisterna magna (CM) administration of 5,7-dihydroxytryptamine (5,7-DHT) failed to attenuate LPS-induced (100 microg/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-[(8beta)-1,6-dimethylergolin-8-yl]methylamine (metergoline) was injected at hour 5 - the time when LPS-treated rats become anorectic. Food intake was measured during the subsequent 2 h. In LPS-treated rats, 8-OH-DPAT (62.5, 125, or 250 microg/kg, sc) injection increased food intake. In a 2 x 2 factorial arrangement of LPS and 8-OH-DPAT, 125 microg/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 intake. However, in a 2 x 2 arrangement of LPS and metergoline, 1 mg/kg metergoline failed to increase food intake in LPS and non-LPS-treated rats in two separate trials. The ability of the 5-HT(1A) receptor agonist 8-OH-DPAT to attenuate LPS-induced anorexia in rats supports a role of 5-HT in LPS-induced anorexia.
Hrupka
B J
BJ
Institute of Animal Sciences, Physiology and Animal Husbandry, Swiss Federal Institute of Technology, Schorenstrasse 16, Postfach, 8603, Schwerzenbach, Switzerland. brian.hrupka@inw.agrl.ethz.ch
Langhans
W
W
D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism; D002946:Cisterna Magna / Q000293:injuries; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides; D008297:Male; D008711:Metergoline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D008070:Lipopolysaccharides; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D008711:Metergoline; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin