The Serotoninergic System in Sleep and Narcolepsy

Abstract

(from the chapter) Over 60 years ago, researchers discovered that a blood-borne substance increased vascular tone and intestinal motility by constricting smooth muscle. They named this substance serotonin based on the Latin word serum and the Greek word tonic, and soon after, this factor was identified as 5-hydroxytryptamine (5-HT). Decades of research have now shown that 5-HT plays a complex and multifaceted role in sleep-wake regulation, and altered 5-HT signaling may underlie some of the symptoms and pathophysiology of narcolepsy. In humans, narcolepsy is caused by loss of the orexin/hypocretin-producing neurons in the lateral hypothalamus. Studies in rodents have demonstrated that orexin promotes arousal, inhibits REM sleep, and regulates transitions between behavioral states. Most importantly, disrupted orexin signaling in animals elicits narcolepsy-like symptoms including chronic sleepiness and cataplexy. The orexin neurons densely innervate most serotonergic nuclei, and in turn, they receive moderately heavy serotonergic inputs. Both orexin and 5-HT are thought to promote wakefulness and inhibit REM sleep, and destruction of either system can result in a narcolepsy-like behavior. For example, in cats, electrolytic lesions of the serotonergic neurons in the rostral raphe nuclei or suppression of neuronal activity in the dorsal raphe nucleus (DRN) can elicit direct transitions from wakefulness to REM sleep. These findings suggest that reduced 5-HT tone may result in symptoms of REM sleep dysregulation typical of narcolepsy, and conversely, increasing 5-HT levels with selective serotonin reuptake inhibitors (SSRIs) improves cataplexy. This chapter reviews how 5-HT normally regulates sleep and wakefulness, and how abnormal 5-HT signaling may contribute to narcolepsy. (PsycINFO Database Record (c) 2012 APA, all rights reserved).