To investigate the effect on the sleep EEG, a 1-mg oral dose of SR 46349B, a novel 5-HTThe pivotal role of serotonin (5-hydroxytryptamine, 5-HT) in sleep regulation has been the mainstay of the monoamine theory of sleep (Jouvet 1972). Although the views about the functions of this neurotransmitter have evolved, there is little doubt about its involvement in sleep mechanisms (McCormick 1992). Serotonergic neurons of the nucleus raphe dorsalis are most active during wakefulness and have been proposed to participate in the build-up of sleep propensity (Adrien 1995). Animal studies revealed that these neurons decrease firing upon transition from wakefulness to nonREM sleep (NREMS), and become quiescent during REM sleep (REMS). Thus, deactivation of the serotonergic system may facilitate the production of NREMS and REMS (Adrien 1995). One of the complexities in accounting for the actions of 5-HT is the large number of different receptors and receptor subtypes. 5-HT receptors are classified into four distinct classes, comprising seven fully characterized functional receptor subtypes and several recombinant receptors (Hoyer and Martin 1996). While the involvement of three main classes (i.e., 5-HT 1 , 5-HT 2 , and 5-HT 3 receptors) in the regulation of sleep and wakefulness has been studied, it is the postsynaptic 5-HT 1A receptor that seems to mediate the inhibition of REMS and the promotion of wakefulness, whereas activation of the 5-HT 2 receptor may exert a tonic inhibition of slow wave sleep (SWS) (see Adrien 1995 for review). In relation to sleep homeostasis, the latter is of particular interest because 5-HT 2 antagonists were shown to increase the amount of SWS and to enhance EEG slow-