Present address: Stanford University, Department of Psychiatry and Behavioural Sciences, 701B Welch Road, Palo Alto, CA 94304, USA.
Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice
Article first published online: 31 MAR 2008
© The Authors (2008)
European Journal of Neuroscience
Volume 27, Issue 7, pages 1793–1800, April 2008
How to Cite
Adamantidis, A., Salvert, D., Goutagny, R., Lakaye, B., Gervasoni, D., Grisar, T., Luppi, P.-H. and Fort, P. (2008), Sleep architecture of the melanin-concentrating hormone receptor 1-knockout mice. European Journal of Neuroscience, 27: 1793–1800. doi: 10.1111/j.1460-9568.2008.06129.x
- Issue published online: 31 MAR 2008
- Article first published online: 31 MAR 2008
- Received 27 November 2007, revised 30 January 2008, accepted 4 February 2008
- lateral hypothalamus;
- melanin-concentrating hormone;
- paradoxical sleep
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.