Blockade of 5-hydroxytryptamine (serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep.

Recent data suggest that interleukin-1-induced enhancement of non-rapid eye movement sleep is mediated, in part, by the serotonergic system. To determine if sleep changes induced by interleukin-1 are mediated by a specific serotonergic receptor subtype, we evaluated interleukin-1 effects on sleep in rats pretreated with the 5-hydroxytryptamine (serotonin)-2 receptor antagonist ritanserin. Ritanserin (0.63 mg/kg, intraperitoneally) by itself did not alter sleep-wake behavior, although it did reduce cortical brain temperature. Interleukin-1 (5 ng, intracerebroventricularly) enhanced non-rapid eye movement sleep, suppressed rapid eye movement sleep, and induced a moderate febrile response. Pretreatment with ritanserin completely blocked the febrile response to interleukin-1 and abolished the interleukin-1-induced enhancement in non-rapid eye movement sleep that occurred during postinjection hours 3-4, without altering interleukin-1 effects on rapid eye movement sleep. The present data suggest that serotonin may partially mediate interleukin-1 effects on sleep by interacting with 5-hydroxytryptamine (serotonin)-2 receptors. These results also suggest that interactions between the serotonergic system and interleukin-1 may be important in regulating sleep-wake behavior.