The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat.
The effects of LP-44, a selective 5-HT7 receptor agonist, and of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of LP-44 (1.25-5.0 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Similar effects were observed after the direct administration into the DRN of SB-269970 (0.5-1.0 mM). Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods. It is proposed that the suppression of REMS after microinjection of LP-44 into the DRN is related, at least in part, to the activation of GABAergic neurons in the DRN that contribute to long projections that reach, among others, the laterodorsal and pedunculopontine tegmental nuclei involved in the promotion of REMS.
Monti
Jaime M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11300, Uruguay. jmonti@mednet.org.uy
Leopoldo
Marcello
M
Jantos
Héctor
H
D000704:Analysis of Variance; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D008297:Male; D010636:Phenols / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012894:Sleep Stages / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects
D001425:Bacterial Outer Membrane Proteins; D055666:Lipopeptides; D008074:Lipoproteins; C417669:Lp44 lipopeptide; D010636:Phenols; C404922:SB 269970; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides