Effects of the 5-HT7 receptor antagonist SB-269970 microinjected into the dorsal raphe nucleus on REM sleep in the rat

The effects of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. SB-269970 was infused directly into the dorsal raphe nucleus (DRN) during the light phase. The 5-HT7 receptor antagonist (0.25–1.0 mM) induced a significant reduction of REM sleep and of the number of REM periods whereas REM sleep latency was augmented. Pretreatment with the GABAA receptor agonist muscimol (1.0–2.0 mM), which by itself did not affect sleep variables, prevented the decrease of REM sleep induced by SB-269970 (1.0 mM).Our results indicate that the 5-HT7 receptor is involved in the effect of DRN serotonergic (5-HT) neurons on brainstem structures that act to promote and induce REM sleep. We propose that the SB-269970-induced suppression of REM sleep is dependent upon the inhibition of GABA release in the DRN.