Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice

Authors

  • Antoine Adamantidis,

    1. 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
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  • Denise Salvert,

    1. CNRS UMR5167, Physiopathologies des Réseaux Neuronaux du Cycle Veille–Sommeil, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France
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  • Romain Goutagny,

    1. CNRS UMR5167, Physiopathologies des Réseaux Neuronaux du Cycle Veille–Sommeil, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France
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  • Bernard Lakaye,

    1. 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
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  • Damien Gervasoni,

    1. CNRS UMR5167, Physiopathologies des Réseaux Neuronaux du Cycle Veille–Sommeil, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France
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  • Thierry Grisar,

    1. 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
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  • Pierre-Hervé Luppi,

    1. CNRS UMR5167, Physiopathologies des Réseaux Neuronaux du Cycle Veille–Sommeil, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France
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  • Patrice Fort

    1. CNRS UMR5167, Physiopathologies des Réseaux Neuronaux du Cycle Veille–Sommeil, Institut Fédératif des Neurosciences de Lyon (IFR 19), Université Claude Bernard Lyon I, 7 Rue Guillaume Paradin, 69372 Lyon Cedex 08, France
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  • *

    Present address: Stanford University, Department of Psychiatry and Behavioural Sciences, 701B Welch Road, Palo Alto, CA 94304, USA.

Dr Antoine Adamantidis, at *present address below, or Dr Patrice Fort, CNRS UMR 5167, 2CNRS UMR5167, as above.
E-mail: tidis@stanford.edu or patrice.fort@sommeil.univ-lyon1.fr

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.

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