title: Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression.
abstract: The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República Montevideo, Uruguay.
authors.forename: Pablo
authors.initials: P
authors.lastname: Torterolo
authors.affiliation: Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable Montevideo, Uruguay.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lagos
authors.affiliation: Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable Montevideo, Uruguay.
authors.forename: Jessika
authors.initials: J
authors.lastname: Urbanavicius
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República Montevideo, Uruguay.
authors.forename: Luciana
authors.initials: L
authors.lastname: Benedetto
authors.affiliation: Department of Physiology, School of Medicine, Universidad de la República Montevideo, Uruguay.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pascovich
authors.affiliation: Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable Montevideo, Uruguay.
authors.forename: Ximena
authors.initials: X
authors.lastname: López-Hill
authors.affiliation: WebSciences International and University of California, Los Angeles School of Medicine Los Angeles, CA, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chase
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Hospital de Clínicas, Universidad de la República Montevideo, Uruguay.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Monti
keywords: MCH; hypothalamus; mood; paradoxical sleep; peptides; raphe; serotonin