Activation of serotonin 5-HT(1B) receptor in the dorsal raphe nucleus affects REM sleep in the rat.
The effects of CP-94253, a selective 5-HT(1B) receptor agonist, and of SB 224-289, a selective 5-HT(1B) receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT(1B) 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 CP-94253 (1-4 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the mean duration of REM episodes. On the other hand, SB 224-289 (0.25-0.5 mM) decreased REMS and the number of REM periods. Pretreatment with SB 224-289 (0.125-0.25 mM) antagonized the CP-94253 (4 mM)-induced reduction of REMS and of the mean duration of REM periods. Administration of the GABA(A) receptor agonist muscimol (1.5mM), which by itself did not significantly affect sleep variables, prevented the effect of CP-94253 (4 mM) on REMS suppression. It is proposed that the suppression of REMS after microinjection of CP-94253 into the DRN is related to the inhibition of GABAergic interneurons that make synaptic contacts with serotonergic cells. The resultant increase of serotonin release at postsynaptic sites involved in the induction and maintenance of REMS would induce the suppression of the behavioral state.
Monti
Jaime M
JM
Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo 11600, Uruguay. jmonti@mednet.org.uy
Jantos
Héctor
H
Lagos
Patricia
P
D000704:Analysis of Variance; D000818:Animals; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004576:Electromyography; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology
C097067:CP 94253; D018755:GABA Agonists; D010881:Piperidones; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011963:Receptors, GABA-A; C108518:SB 22489G; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D009118:Muscimol