Serotonin and the sleep/wake cycle: special emphasis microdialysis studies

Several areas in the brainstem and forebrain are important for the modulati on and expression of the sleep/wake cycle. Even if the first observations o f biochemical events in relation to sleep were made only 40 rears ago, it i s now well established that several neurotransmitters. neuropeptides, and n eurohormones are involved in the modulation of the sleep/wake cycle. Serotonin has been known for many years to play a role in the modulation of sleep. however, it is still very controversial how and where serotonin may operate this modulation. Early studies suggested that serotonin is necessa ry to obtain and maintain behavioral sleep (permissive role on sleep). However, more recent microdialysis experiments provide evidence that the le vel of serotonin during W is higher in most cortical and subcortical areas receiving serotonergic projections. In this view the level of extracellular serotonin would be consistent with the pattern of discharge of the DRN ser otonergic neurons which show the highest firing rate during W, followed by a decrease in slow wave sleep and by virtual electrical silence during REM sleep. This suggests that during waking serotonin may complement the action of nor adrenaline and acelylcholine in promoting cortical responsiveness and parti cipate to the inhibition of REM-sleep effector neurons in the brainstem (in hibitory role on REM sleep). The apparent inconsistency between an inhibitory and a facilitatory role pl ayed by serotonin on sleep has at least two possible explanations. On the o ne hand serotonergic modulation on the sleep/wake cycle takes place through a multitude of post-synaptic receptors which mediate different or even opp osite responses; on the other hand the achievement of a behavioral state de pends on the complex interaction between the serotonergic and other neurotr ansmitter systems. The main aim of this commentary is to review the role of brain serotonin in relation to the sleep/wake cycle. In particular we highlight the importanc e of microdialysis for on-line monitoring of the level of serotonin in diff erent areas of the brain across the sleep/wake cycle. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.