Parenteral administration of the serotonin-1 agonist eltoprazine (0.0625 to 4.0 mglkg [0.0002 to 0.016 mmollkgJ) in freely moving cats produced significant suppression of electrophysiologic rapid eye movement (REM) sleep signs, ponto-geniculo-occipital (PGG) activity, and REM sleep behavior. The virtual total suppression of REM sleep (0.4%, 4.0 mglkg) and PGG wave activity (2 to 4 mglkg) in exchange for increasing amounts of non-REM (NREM) slow-wave sleep was a dose-dependent function of the amount of eltoprazine KEY WORDS: REM sleep; PGG waves; Serotonin; Eltoprazine Despite the large number of studies implicating sero tonin (5-HT) in the modulation of behavioral state, its exact role in the regulation of sleep and waking remains unclear. Pharmacological studies designed to elucidate the mechanism by which 5-HT neurotransmission aff ects behavioral state have reported paradoxical or contradictory results. While the listing of multiple 5-HT receptor subtypes (Glennon 1986;Peroutka 1988) has elucidated many of the pharmacological properties of ser otonin and underscores the complexity of its modula tory influences, this research has failed to provide a detailed understanding of behavioral state control and administered. Wakefulness was unaffected by eltoprazine regardless of dose. Concurrent with this dose-dependent suppression of REM was a dose-dependent increase in electroencephalographic synchrony and mean electromyographic amplitude. Since eltoprazine was found to shift the balance between REM and NREM sleep but did not change the balance between sleep and waking, it is a potentially useful tool for the investigation of serotonergic-cholinergic interaction.lNeuropsychopharmacology 8:7-13, 1993J neurophysiological phenomena. One reason for this failure is that surprisingly few studies have focused on how administration of receptor-specifIc 5-HT agonists affects sleep, particularly rapid eye movement (REM) sleep.We have previously observed suppression of REM sleep by the parenteral administration of the 5-HTl agonist eltoprazine (Quattrochi et al. 1990) and docu mented the REM rebound that followed discontinua tion of the drug. These findings support the hypothe sis that REM sleep is under the inhibitory control of serotonin (Hobson and Steriade 1986). We now dem onstrate that the suppression of REM sleep is dose de pendent and show that the dose-response properties of one relatively specifIc REM sleep sign, ponto geniculo-occipital (PGO) waves, are quantitatively sen sitive to eltoprazine.PGO waves are of particular interest because they are highly specifIc phenomena of REM sleep. Early studies by Jouvet (1969), Delorme et al. (1965), and De ment et al. (1973) indicated that PGO activity was sus ceptible to serotonergic inhibition; successive studies
