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Immunoneutralization of Melanin-Concentrating Hormone (MCH) in the Dorsal Raphe Nucleus: Effects on Sleep and Wakefulness

Immunoneutralization of Melanin-Concentrating Hormone (MCH) in the Dorsal Raphe Nucleus: Effects on Sleep and Wakefulness

Patricia Lagos, Pablo Torterolo, Héctor Jantos, Jaime M Monti

Brain Res. 2011 Jan 19;1369:112-8.

PMID: 21078307

Abstract:

Hypothalamic neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator exert a positive control over energy homeostasis, inducing feeding and decreasing metabolism. Recent studies have shown also that this system plays a role in the generation and/or maintenance of sleep. MCHergic neurons project to the serotonergic dorsal raphe nucleus (DR), a neuroanatomical structure involved in several functions during wakefulness (W), and in the regulation of rapid-eye movements (REM) sleep. Recently, we determined the effect of MCH microinjected into the DR on sleep variables in the rat. MCH produced a marked increment of REM sleep, whereas slow wave sleep (SWS) showed only a moderate increase. In the present study, we analyze the effect of immunoneutralization of MCH in the DR on sleep and W in the rat. Compared to the control solution, microinjections of anti-MCH antibodies (1/100 solution in 0.2 μl) induced a significant increase in REM sleep latency (31.2±7.1 vs. 84.2±24.8 min, p<0.05) and a decrease of REM sleep time (37.8±5.4 vs. 17.8±2.9 min, p<0.05) that was related to the reduction in the number of REM sleep episodes. In addition, there was an increase of total W time (49.8±4.6 vs. 72.0±5.7 min, p<0.01). Light sleep and SWS remained unchanged. The intra-DR administration of a more diluted solution of anti-MCH antibodies (1/500) or rabbit pre-immune serum did not modify neither W nor REM sleep variables. Our findings strongly suggest that MCH released in the DR facilitates the occurrence of REM sleep.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248220	Anti-MCH antibody produced in rabbit			Price

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