title: Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice.
abstract: Growing amounts of data indicate involvement of the posterior hypothalamus in the regulation of sleep, especially paradoxical sleep (PS). Accordingly, we previously showed that the melanin-concentrating hormone (MCH)-producing neurons of the rat hypothalamus are selectively activated during a PS rebound. In addition, intracerebroventricular infusion of MCH increases total sleep duration, suggesting a new role for MCH in sleep regulation. To determine whether activation of the MCH system promotes sleep, we studied spontaneous sleep and its homeostatic regulation in mice with deletion of the MCH-receptor 1 gene (MCH-R1-/- vs. MCH-R1+/+) and their behavioural response to modafinil, a powerful antinarcoleptic drug. Here, we show that the lack of functional MCH-R1 results in a hypersomniac-like phenotype, both in basal conditions and after total sleep deprivation, compared to wild-type mice. Further, we found that modafinil was less potent at inducing wakefulness in MCH-R1-/- than in MCH-R1+/+ mice. We report for the first time that animals with genetically inactivated MCH signaling exhibit altered vigilance state architecture and sleep homeostasis. This study also suggests that the MCH system may modulate central pathways involved in the wake-promoting effect of modafinil.
authors.affiliation: Research Center for Cellular and Molecular Neurobiology, Unit of Molecular Neurophysiology, University of Liège, 1 Avenue de l'Hôpital, Bat. B-36, 4000 Liège, Belgium. tidis@stanford.edu
authors.forename: Antoine
authors.initials: A
authors.lastname: Adamantidis
authors.forename: Denise
authors.initials: D
authors.lastname: Salvert
authors.forename: Romain
authors.initials: R
authors.lastname: Goutagny
authors.forename: Bernard
authors.initials: B
authors.lastname: Lakaye
authors.forename: Damien
authors.initials: D
authors.lastname: Gervasoni
authors.forename: Thierry
authors.initials: T
authors.lastname: Grisar
authors.forename: Pierre-Hervé
authors.initials: PH
authors.lastname: Luppi
authors.forename: Patrice
authors.initials: P
authors.lastname: Fort
mesh_terms: D000818:Animals; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D014851:Wakefulness / Q000235:genetics
chemical_list: C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin