title: Immunoneutralization of melanin-concentrating hormone (MCH) in the dorsal raphe nucleus: effects on sleep and wakefulness.
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.
authors.affiliation: Department of Physiology, School of Medicine, University of the Republic, Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lagos
authors.forename: Pablo
authors.initials: P
authors.lastname: Torterolo
authors.forename: Héctor
authors.initials: H
authors.lastname: Jantos
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Monti
mesh_terms: D000818:Animals; D007028:Hypothalamic Hormones / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008543:Melanins / Q000378:metabolism* / Q000494:pharmacology; D008845:Microinjections; D010907:Pituitary Hormones / Q000378:metabolism* / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone