Vagal CCK and 5-HT3receptors are unlikely to mediate LPS or IL-1β-induced fever

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT3receptors in the febrile response after intraperitoneal human recombinant interleukin-1β (IL-1β) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 μg/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT3 receptor (ondansetron HCl; 100 μg/kg) or the CCK-A receptor (L-364,718, 100 or 200 μg/kg) in combination with LPS or IL-1β. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1β- or LPS-induced fever. Neither activation of 5-HT3 receptors nor blockade of 5-HT3 receptors affected body temperature or LPS fever. Taken to...