Effect of the selective activation of serotonin 5-HT3 receptors on sleep and waking

Abstract

The 5-HT3 receptor is a ligand-gated ion channel that belongs to the Cys-loop family, which also includes receptors such as the nicotinic acetylcholine receptor. As other 5-HT receptors subtypes, the 5-HT3 receptor seems to be involved in a large range of physiological processes, among of them sleep. Its role in the sleep-wake physiology has not been clearly established until now, but several pieces of evidence show its activation effect on wakefulness and inhibitory effect on slow-wave sleep. In addition, the 5-HT3 receptors seem to be implicated in circadian rhythm regulation and in REM sleep propensity. Many studies highlight its role in sleep disorders and more precisely in obstructive sleep apnea (OSA) and in fibromyalgia. Its effects in OSA are double. Indeed, 5-HT3 receptor antagonists increase respiration both at the central and the peripheral levels, and thus are potential therapeutic drugs for OSA. Drugs acting on 5-HT transmission have brought interesting results in animal models of apnea syndrome, as well as in patients with OSA. However, results are still disappointing since, in contrast to nasal continuous positive airway pressure that suppress nearly all respiratory events, drugs only lower the respiratory disturbance index by about 20-50%. Chronic pain that relates to inflammatory processes implicates 5-HT 3 neurotransmission, and there is some evidence that the 5-HT 3 receptor antagonist tropisetron had beneficial effects on pain intensity and sleep disturbance in patients with fibromyalgia. © 2008 Birkhäuser Verlag AG.