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Sleep architecture of the melanin‐concentrating hormone receptor 1‐knockout mice
Author(s) -
Adamantidis Antoine,
Salvert Denise,
Goutagny Romain,
Lakaye Bernard,
Gervasoni Damien,
Grisar Thierry,
Luppi PierreHervé,
Fort Patrice
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06129.x
Subject(s) - melanin concentrating hormone , modafinil , wakefulness , endocrinology , sleep deprivation , hypothalamus , medicine , sleep (system call) , narcolepsy , knockout mouse , vigilance (psychology) , hormone , rapid eye movement sleep , biology , receptor , neuroscience , circadian rhythm , neuropeptide , pharmacology , eye movement , electroencephalography , computer science , operating system
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.