Melanin-concentrating hormone in the Locus Coeruleus aggravates helpless behavior in stressed rats.

Autor: Urbanavicius J; Departament of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Uruguay., Fabius S; Departament of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Uruguay., Roncalho A; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Joca S; Department of Physics and Chemistry, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, Brazil., Torterolo P; Department of Physiology, School of Medicine, Universidad de la República, Montevideo, Uruguay., Scorza C; Departament of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Uruguay. Electronic address: cscorza@iibce.edu.uy.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2019 Nov 18; Vol. 374, pp. 112120. Date of Electronic Publication: 2019 Jul 31.
DOI: 10.1016/j.bbr.2019.112120
Abstrakt: Animal studies have shown that antagonists of receptor 1 of Melanin-Concentrating Hormone (MCH-R1) elicit antidepressive-like behavior, suggesting that MCH-R1 might be a novel target for the treatment of depression and supports the hypothesis that MCHergic signaling regulates depressive-like behaviors. Consistent with the evidence that MCHergic neurons send projections to dorsal and median raphe nuclei, we have previously demonstrated that MCH microinjections in both nuclei induced a depressive-like behavior. Even though MCH neurons also project to Locus Coeruleus (LC), only a few studies have reported the behavioral and neurochemical effect of MCH into the LC. We studied the effects of MCH (100 and 200 ng) into the LC on coping-stress related behaviors associated with depression, using two different behavioral tests: the forced swimming test (FST) and the learned helplessness (LH). To characterize the functional interaction between MCH and the noradrenergic LC system, we also evaluated the neurochemical effects of MCH (100 ng) on the extracellular levels of noradrenaline (NA) in the medial prefrontal cortex (mPFC), an important LC terminal region involved in emotional processing. MCH administration into the LC elicited a depressive-like behavior evidenced in both paradigms. Interestingly, in the LH, MCH (100) elicited a significant increase in escape failures only in stressed animals. A significant decrease in prefrontal levels of NA was observed after MCH microinjection into the LC. Our results demonstrate that increased MCH signaling into the LC triggers depressive-like behaviors, especially in stressed animals. These data further corroborate the important role of MCH in the neurobiology of depression.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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