Interleukin-1β enhances non-rapid eye movement sleep when microinjected into the dorsal raphe nucleus and inhibits serotonergic neurons in vitro

Abstract

Interleukin-1 (IL-1) and IL-1 receptors are constitutively expressed in normal brain. IL-1 increases non-rapid eye movements (NREM) sleep in several animal species, an effect mediated in part by interactions with the serotonergic system. The site(s) in brain at which interactions between IL-1 and the serotonergic system increase NREM sleep remain to be identified. The dorsal raphe (DRN) is the origin of the major ascending serotonergic pathways to the forebrain, and it contains IL-1 receptors. This study examined the hypothesis that IL-1 increases NREM sleep by acting at the level of the DRN. IL-1β (0.25 and 0.5 ng) was microinjected into the DRN of freely behaving rats and subsequent effects on sleep–wake activity were determined. IL-1β 0.5 ng increased NREM sleep during the first 2 h post-injection from 33.5 ± 3.7% after vehicle microinjection to 42.9 ± 3.0% of recording time. To determine the effects of IL-1β on electrophysiological properties of DRN serotonergic neurons, intracellular recordings were performed in a guinea-pig brain stem slice preparation. In 26 of 32 physiologically and pharmacologically identified serotonergic neurons, IL-1β superfusion (25 ng/mL) decreased spontaneous firing rates by 50%, from 1.6 ± 0.2 Hz (before IL-1β superfusion) to 0.8 ± 0.2 Hz. This effect was reversible upon washout. These results show that IL-1β increases NREM sleep when administered directly into the DRN. Serotonin enhances wakefulness and these novel data also suggest that IL-1β-induced enhancement of NREM sleep could be due in part to the inhibition of DRN serotonergic neurons.