It has been known for some years that the functional activity of 5-HT neurons in the brain changes dramatically during the sleep-wake arousal cycle. Thus from a stable, slow and regular discharge pattern during quiet wakening, neuronal activity gradually declines as the animal becomes drowsy and enters slow-wave sleep. During rapid eye movement (REM) sleep, 5-HT activity is totally suppressed but in anticipation of awakening the neuronal activity returns to its basal level several seconds before the end of the REM episode. During arousal or wakening, the 5-HT neuronal discharge pattern increases considerably above the quiet waking state.
Koella has reviewed the evidence implicating the involvement of serotonin in the sleep-wake cycle but the involvement of specific serotonin receptor subtypes in sleep mechanisms is unclear. Experimental evidence suggests that 5-HT1A agonists delay the onset of REM sleep while 5-HT2 antagonists suppress REM and have variable effects on non-REM sleep.
It must be emphasized that most studies of the relationship between the serotonergic system and sleep have been conducted in rats and therefore the relevance of such findings to man remains unproven. From such experimental studies, it has been shown that blockade of 5-HT2 receptors increases the proportion of slow-wave sleep and decreases the quantity of REM sleep. Whether this effect of 5-HT2 antagonists can be ascribed to a specific effect on slow-wave sleep is, however, a matter of conjecture as any increase in time spent in one stage of sleep will be reflected in a decrease in the time spent in other stages of sleep. However, experimental evidence suggests that most drugs that alter serotonergic transmission reduce REM sleep. There is evidence that the 5-HT2 antagonist ritanserin improves sleep quality in those suffering from ''jet lag'' which suggests that the 5-HT2 receptors may be involved in adjusting the sleep-wake cycle to the photoperiod. Furthermore, experimental data suggest that activation of 5-HT2 receptors may vary according to the sleep-wake cycle. Such findings suggest that 5-HT2 receptors are involved in the regulation of circadian rhythms and the sleep-wake cycle. With regard to the overall role of 5-HT in sleep, Koella has postulated that serotonin may produce its various effects on sleep architecture by influencing cognition and vigilance.
Details of the effects of psychotropic drugs on the sleep profile are discussed in Chapter 10.
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