Abnormal response of melanin-concentrating hormone deficient mice to fasting

Hyperactivity and rapid eye movement sleep suppression

J. T. Willie, C. M. Sinton, E. Maratos-Flier, Masashi Yanagisawa

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that has been implicated in energy homeostasis. Pharmacological studies with MCH and its receptor antagonists have suggested additional behavioral roles for the neuropeptide in the control of mood and vigilance states. These suggestions have been supported by a report of modified sleep in the MCH-1 receptor knockout mouse. Here we found that MCH knockout (MCH-/-) mice slept less during both the light and dark phases under baseline conditions. In response to fasting, MCH-/- mice exhibited marked hyperactivity, accelerated weight loss and an exaggerated decrease in rapid eye movement (REM) sleep. Following a 6-h period of sleep deprivation, however, the sleep rebound in MCH-/- mice was normal. Thus MCH-/- mice adapt poorly to fasting, and their loss of bodyweight under this condition is associated with behavioral hyperactivity and abnormal expression of REM sleep. These results support a role for MCH in vigilance state regulation in response to changes in energy homeostasis and may relate to a recent report of initial clinical trials with a novel MCH-1 receptor antagonist. When combined with caloric restriction, the treatment of healthy, obese subjects with this compound resulted in some subjects experiencing vivid dreams and sleep disturbances.

Original languageEnglish (US)
Pages (from-to)819-829
Number of pages11
JournalNeuroscience
Volume156
Issue number4
DOIs
StatePublished - Oct 28 2008

Fingerprint

REM Sleep
Fasting
Sleep
Neuropeptides
Homeostasis
Caloric Restriction
Sleep Deprivation
melanin-concentrating hormone
Knockout Mice
Weight Loss
Healthy Volunteers
Clinical Trials
Pharmacology
Light
melanin-concentrating hormone receptor

Keywords

  • hypocretin
  • lateral hypothalamus
  • locomotor activity
  • NGD-4715
  • orexin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Abnormal response of melanin-concentrating hormone deficient mice to fasting : Hyperactivity and rapid eye movement sleep suppression. / Willie, J. T.; Sinton, C. M.; Maratos-Flier, E.; Yanagisawa, Masashi.

In: Neuroscience, Vol. 156, No. 4, 28.10.2008, p. 819-829.

Research output: Contribution to journalArticle

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