Changes in sleep and wakefulness following 5-HT1A ligands given systemically and locally in different brain regions.

Serotonin (5-HT) has been implicated in the regulation of vigilance, but whether 5-HT is important for sleep or waking processes remains controversial. This review addresses the role of 5-HT1A receptors in sleep and wakefulness. Systemic administration of 5-HT1A agonists consistently increases wakefulness, whereas slow wave sleep (SWS) and REM (rapid-eye movement) sleep are reduced. However, systemic 5-HT1A agonists also produce a delayed increase in deep slow wave sleep, or an increase in slow wave activity. Intrathecal administration of a selective 5-HT1A agonist produces an increase in SWS, whereas wakefulness is reduced, presumably by stimulating 5-HT1A receptors located presynaptically on primary afferents in the spinal cord. Microinjection of serotonin into the region of the cholinergic basalis neurons produces an increase in slow wave activity, presumably by stimulating 5-HT1A receptors. Microdialysis perfusion of a selective 5-HT1A agonist into the dorsal Raphe nucleus causes an increase in REM sleep, whereas the other sleep/wake stages are unaltered. The REM sleep increase is likely due to a decrease in 5-HT neuronal activity, and thereby reduced 5-HT neurotransmission in projection areas, e.g. the laterodorsal and pedunculopontine tegmental nuclei. Direct injection of a selective 5-HT1A agonist into the pedunculopontine tegmental nuclei reduces REM sleep, consistent with such a hypothesis. These complex sleep/wake data of 5-HT1A ligands suggest that 5-HT1A receptor activation may increase waking, increase slow wave sleep or increase REM sleep depending on where the 5-HT1A receptors are located within the central nervous system.