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

Adamantidis, Antoine Roger; Salvert, Denise; Goutagny, Romain; Lakaye, Bernard; Gervasoni, Damien; Grisar, Thierry; Luppi, Pierre-Hervé; Fort, Patrice (2008). Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice. European journal of neuroscience, 27(7), pp. 1793-1800. Blackwell Science 10.1111/j.1460-9568.2008.06129.x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Adamantidis, Antoine Roger

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0953-816X

Publisher:

Blackwell Science

Language:

English

Submitter:

Stefanie Hetzenecker

Date Deposited:

11 Jul 2018 15:43

Last Modified:

23 Oct 2019 07:21

Publisher DOI:

10.1111/j.1460-9568.2008.06129.x

PubMed ID:

18380672

BORIS DOI:

10.7892/boris.117272

URI:

https://boris.unibe.ch/id/eprint/117272

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