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.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Willie JT,Sinton CM,Maratos-Flier E,Yanagisawa Mdoi
10.1016/j.neuroscience.2008.08.048subject
Has Abstractpub_date
2008-10-28 00:00:00pages
819-29issue
4eissn
0306-4522issn
1873-7544pii
S0306-4522(08)01280-3journal_volume
156pub_type
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