Effects of the 5-HT(7) receptor antagonist SB-269970 microinjected into the dorsal raphe nucleus on REM sleep in the rat.
The effects of SB-269970, a selective 5-HT(7) 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-HT(7) 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 GABA(A) 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-HT(7) 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.
Monti
Jaime M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11300, Uruguay. jmonti@mednet.org.uy
Jantos
Héctor
H
D000704:Analysis of Variance; D000818:Animals; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010636:Phenols / Q000008:administration & dosage*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D012895:Sleep, REM / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018755:GABA Agonists; D010636:Phenols; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D009118:Muscimol; D005680:gamma-Aminobutyric Acid