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 serot onergic agonists and antagonists to alter the hypophagic responses to IL-1 and bacterial lipopolysaccharide (LPS). Hypophagia was assessed in ad Lib-f ed mice by recording the intake of sweetened milk in a 30-min period. Acute intraperitoneal administration of mouse IL-1 beta reliably decreased milk intake. This hypophagic response was not affected by any of the serotonin a ntagonists tested, including 5-HT1A (WAY100135 and propranolol), 5-HT1B (GR 127935), 5-HT2 (ritanserin, ketanserin, SB206553, and RS102221), mixed 5-HT 1/2 (methysergide and metergoline), and 5-HT3 (tropisetron) receptor antago nists. The 5-HT1A agonists (8-OH-DPAT and ipsapirone) and a 5-HT1B agonist (CGS12066B) known to decrease the activity of serotonergic neurons, also ha d no effect. Mice pretreated with 5,7-dihydroxytryptamine to deplete brain serotonin ate less, but, nevertheless, displayed similar hypophagic respons es to mIL-1 beta or LPS. The results suggest that serotonin is not involved in the decrease in short-term milk intake induced by mIL-1 beta or LPS in mice that have been fed ad lib. (C) 2000 Elsevier Science Inc.