Lack of evidence for a role of serotonin in interleukin-1-induced hypophagia.
Interleukin-1 (IL-1) administration depresses food intake in rodents. IL-1 is known to increase the metabolism of serotonin, which is known to affect feeding behavior. Thus, serotonin is an obvious candidate for a mediator of the hypophagic response to IL-1. Therefore, we tested the ability of serotonergic agonists and antagonists to alter the hypophagic responses to IL-1 and bacterial lipopolysaccharide (LPS). Hypophagia was assessed in ad lib-fed mice by recording the intake of sweetened milk in a 30-min period. Acute intraperitoneal administration of mouse IL-1beta reliably decreased milk intake. This hypophagic response was not affected by any of the serotonin antagonists tested, including 5-HT(1A) (WAY100135 and propranolol), 5-HT(1B) (GR127935), 5-HT(2) (ritanserin, ketanserin, SB206553, and RS102221), mixed 5-HT(1/2) (methysergide and metergoline), and 5-HT(3) (tropisetron) receptor antagonists. The 5-HT(1A) agonists (8-OH-DPAT and ipsapirone) and a 5-HT(1B) agonist (CGS12066B) known to decrease the activity of serotonergic neurons, also had no effect. Mice pretreated with 5,7-dihydroxytryptamine to deplete brain serotonin ate less, but, nevertheless, displayed similar hypophagic responses to mIL-1beta or LPS. The results suggest that serotonin is not involved in the decrease in short-term milk intake induced by mIL-1beta or LPS in mice that have been fed ad lib.
Swiergiel
A H
AH
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, LA, USA.
Dunn
A J
AJ
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004435:Eating / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; C081293:WAY 100135; C090701:GR 127935; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin