title: Contribution of melanin-concentrating hormone (MCH1) receptor to thermoregulation and sleep stabilization: evidence from MCH1 (-/-) mice.
abstract: Recent studies have explored the implication of melanin-concentrating hormone (MCH) in the process of vigilance states. The current experiments were carried out in mice lacking the MCH(1) receptor (-/-) and wild-type (WT) littermates, to assess the role of MCH(1) receptor in the regulation of sleep architecture, body temperature (BT) and locomotor activity (LMA) under normal condition and following a 1h restraint stress at lights onset. Under baseline conditions, MCH(1) (-/-) mice exhibited consistent changes in waking and sleeping time across the 24-h recording period. We found an increase in the amount of wakefulness (MCH(1) (-/-) 680.1 ± 15.3 min vs. WT, 601.9 ± 18.1, p<0.05) at the expense of total duration of non rapid eye movement (NREM) sleep (MCH(1) (-/-) 664.1 ± 13.9 min vs. WT 750.1 ± 18.5, p<0.05). Additionally, MCH(1) (-/-) mice had a higher mean basal body temperature (MCH(1) (-/-), 36.6 ± 0.1°C vs. WT, 36.0 ± 0.1°C, p<0.05), particularly during the light-resting period. Restraint stress resulted in an immediate increase in wakefulness with a concomitant reduction in NREM sleep and REM sleep in both genotypes, followed by a homeostatic rebound sleep. A concomitant long lasting increase in BT, independently of the behavioural state accompanied those changes in both genotypes. The elevated basal body temperature and reduction in NREM sleep time resulting from shorter NREM episode durations observed in MCH(1) (-/-) suggests that central MCH(1) receptor has a role in thermoregulation and presumably stabilization of NREM sleep.
authors.affiliation: Janssen Pharmaceutical Companies of Johnson & Johnson, Dept. of Neurosciences, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. aahnaou@prd.jnj.com
authors.forename: A
authors.initials: A
authors.lastname: Ahnaou
authors.forename: F M
authors.initials: FM
authors.lastname: Dautzenberg
authors.forename: H
authors.initials: H
authors.lastname: Huysmans
authors.forename: T
authors.initials: T
authors.lastname: Steckler
authors.forename: W H I M
authors.initials: WH
authors.lastname: Drinkenburg
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D004569:Electroencephalography; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin