Effects of the selective activation of 5-HT3 receptors on sleep: a polysomnographic study in healthy volunteers

Abstract The respective role of various classes of central serotonin (5-HT) receptors in the regulation of sleep–wakefulness cycles has been the subject of many studies. Notably, it has been reported that 5-HT 1A/B receptors are involved in the regulation of rapid eye movement sleep (REMS) and that 5-HT 2A/C receptors participate in the control of slow wave sleep (SWS), but the role of 5-HT 3 receptors is less well characterised. In this study we investigated the effects of SR 57227A, a potent and selective 5-HT 3 agonist, on the sleep EEG of normal young male volunteers. SR 57227A (2.5, 5, 10, 20, 40 mg o.d. and 20 mg b.i.d.) or placebo were administered during 7 consecutive days in seven groups of ten subjects using a parallel group design. Sleep EEG recordings were performed on days 6 and 7 after an habituation session. SR 57227A produced a dose-dependent shift of REMS toward the end of the night without changing REMS and SWS duration nor altering sleep continuity. It suggests a role for the 5-HT 3 receptor in the human sleep–wakefulness cycle and particularly in REMS regulation.