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Activation of Melanocortin-4 Receptor Inhibits Both Neuroinflammation Induced by Early Exposure to Ethanol and Subsequent Voluntary Alcohol Intake in Adulthood in Animal Models: Is BDNF the Key Mediator?

dc.contributor.authorFlores-Bastías O.
dc.contributor.authorAdriasola-Carrasco A.
dc.contributor.authorKarahanian E.
dc.date.accessioned2020-09-02T22:17:53Z
dc.date.available2020-09-02T22:17:53Z
dc.date.issued2020
dc.identifier10.3389/fncel.2020.00005
dc.identifier.citation14, , -
dc.identifier.issn16625102
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4485
dc.descriptionThe concept that neuroinflammation induced by excessive alcohol intake in adolescence triggers brain mechanisms that perpetuate consumption has strengthened in recent years. The melanocortin system, composed of the melanocortin 4 receptor (MC4R) and its ligand α-melanocyte-stimulating hormone (α-MSH), has been implicated both in modulation of alcohol consumption and in ethanol-induced neuroinflammation decrease. Chronic alcohol consumption in adolescent rats causes a decrease in an α-MSH release by the hypothalamus, while the administration of synthetic agonists of MC4R causes a decrease in neuroinflammation and a decrease in voluntary alcohol consumption. However, the mechanism that connects the activation of MC4R with the decrease of both neuroinflammation and voluntary alcohol consumption has not been elucidated. Brain-derived neurotrophic factor (BDNF) has been implicated in alcohol drinking motivation, dependence and withdrawal, and its levels are reduced in alcoholics. Deficiencies in BDNF levels increased ethanol self-administration in rats. Further, BDNF triggers important anti-inflammatory effects in the brain, and this could be one of the mechanisms by which BDNF reduces chronic alcohol intake. Interestingly, MC4R signaling induces BDNF expression through the activation of the cAMP-responsive element-binding protein (CREB). We hypothesize that ethanol exposure during adolescence decreases the expression of α-MSH and hence MC4R signaling in the hippocampus, leading to a lower BDNF activity that causes dramatic changes in the brain (e.g., neuroinflammation and decreased neurogenesis) that predispose to maintain alcohol abuse until adulthood. The activation of MC4R either by α-MSH or by synthetic agonist peptides can induce the expression of BDNF, which would trigger several processes that lead to lower alcohol consumption. © Copyright © 2020 Flores-Bastías, Adriasola-Carrasco and Karahanian.
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.subjectalcohol use disorder
dc.subjectalcoholism
dc.subjectbrain-derived neurotrophic factor
dc.subjectMC4R
dc.subjectmelanocyte-stimulating hormone
dc.subjectα-MSH
dc.subjectadenylate cyclase
dc.subjectalpha intermedin
dc.subjectbrain derived neurotrophic factor
dc.subjectbrain derived neurotrophic factor receptor
dc.subjectcyclic AMP
dc.subjectcyclic AMP dependent protein kinase
dc.subjectcyclic AMP responsive element binding protein
dc.subjectcytochrome P450 2E1
dc.subjectimmunoglobulin enhancer binding protein
dc.subjectinterleukin 10
dc.subjectinterleukin 1beta
dc.subjectinterleukin 6
dc.subjectmelanocortin 4 receptor
dc.subjectperoxisome proliferator activated receptor gamma
dc.subjectreduced nicotinamide adenine dinucleotide phosphate oxidase
dc.subjecttransforming growth factor beta1
dc.subjecttumor necrosis factor
dc.subjectadolescence
dc.subjectadulthood
dc.subjectalcohol consumption
dc.subjectalcohol withdrawal syndrome
dc.subjectalcoholism
dc.subjectanimal model
dc.subjectantiinflammatory activity
dc.subjectastrocyte
dc.subjectcognition
dc.subjectdrinking behavior
dc.subjecthippocampus
dc.subjecthypothalamus
dc.subjectinnate immunity
dc.subjectlong term exposure
dc.subjectlong term potentiation
dc.subjectmemory consolidation
dc.subjectmicroglia
dc.subjectnerve cell
dc.subjectnervous system development
dc.subjectnervous system inflammation
dc.subjectneuroapoptosis
dc.subjectneurobiology
dc.subjectnonhuman
dc.subjectprefrontal cortex
dc.subjectReview
dc.subjectsignal transduction
dc.subjectunderage drinking
dc.titleActivation of Melanocortin-4 Receptor Inhibits Both Neuroinflammation Induced by Early Exposure to Ethanol and Subsequent Voluntary Alcohol Intake in Adulthood in Animal Models: Is BDNF the Key Mediator?
dc.typeReview


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