Abnormal response of melanin-concentrating hormone deficient mice to fasting: Hyperactivity and rapid eye movement sleep suppression

• Published in: Neuroscience Vol. 156; no. 4; pp. 819 - 829
• Main Authors: Willie, J.T, Sinton, C.M, Maratos-Flier, E, Yanagisawa, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 28.10.2008; Elsevier
• Subjects: Analysis of Variance; Animals; Behavior, Animal; Biological and medical sciences; Body Composition - genetics; Electroencephalography - methods; Electromyography - methods; Fasting - physiology; Fundamental and applied biological sciences. Psychology; Hyperkinesis - genetics; hypocretin; Hypothalamic Hormones - deficiency; Hypothalamic Hormones - genetics; lateral hypothalamus; locomotor activity; Melanins - deficiency; Melanins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - genetics; Neurology; NGD-4715; orexin; Pituitary Hormones - deficiency; Pituitary Hormones - genetics; Sleep, REM - genetics; Sleep, REM - physiology; Sleep. Vigilance; Spectrum Analysis; Vertebrates: nervous system and sense organs; Wakefulness - genetics; lateral hypothalamus; NREM; melanin-concentrating hormone; rapid eye movement; analysis of variance; ANOVA; FFT; neuropeptide E1; non-rapid eye movement; NGD-4715; orexin; NE1; EMG; electroencephalography; hypothalamic–pituitary–adrenal; EEG; neuropeptide GE; NGE; nuclear magnetic resonance; fast Fourier transform; NMR; MCH; electromyography; hypocretin; HPA; locomotor activity; REM; Fasting; Rodentia; Central nervous system; Lateral hypothalamus; Rapid eye movement sleep; Neuropeptide; Encephalon; Locomotion; Vertebrata; Mammalia; Mouse; Animal; Melanin concentrating hormone; Orexin; NGD- 4715
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.08.048

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.