Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice.
The involvement of 5-HT1B receptors in the regulation of vigilance states was assessed by investigating the spontaneous sleep-waking cycles and the effects of 5-HT receptor ligands on sleep in knock-out (5-HT1B-/-) mice that do not express this receptor type. Both 5-HT1B-/- and wild-type 129/Sv mice exhibited a clear-cut diurnal sleep-wakefulness rhythm, but knock-out animals were characterized by higher amounts of paradoxical sleep and lower amounts of slow-wave sleep during the light phase and by a lack of paradoxical sleep rebound after deprivation. In wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969 (0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935 (0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep. In addition, pretreatment with GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects of both 5-HT1B agonists. In contrast, none of the 5-HT1B receptor ligands, at the same doses as those used in wild-type mice, had any effect on sleep in 5-HT1B-/- mutants. Finally, the 5-HT1A agonist 8-OH-DPAT (0.2-1.2 mg/kg, s.c.) induced in both strains a reduction in the amount of paradoxical sleep. Altogether, these data indicate that 5-HT1B receptors participate in the regulation of paradoxical sleep in the mouse.
Boutrel
B
B
Institut National de la Santé et de la Recherche Médicale U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, 75634 Paris Cedex 13, France.
Franc
B
B
Hen
R
R
Hamon
M
M
Adrien
J
J
D000704:Analysis of Variance; D000818:Animals; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012892:Sleep Deprivation; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole