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Different molecular/behavioral endophenotypes in C57BL/6J mice predict the impact of OX1 receptor blockade on binge-like ethanol intake

dc.contributor.authorAlcaraz-Iborra M.
dc.contributor.authorNavarrete F.
dc.contributor.authorRodríguez-Ortega E.
dc.contributor.authorde la Fuente L.
dc.contributor.authorManzanares J.
dc.contributor.authorCubero I.
dc.date.accessioned2020-09-02T22:11:04Z
dc.date.available2020-09-02T22:11:04Z
dc.date.issued2017
dc.identifier10.3389/fnbeh.2017.00186
dc.identifier.citation11, , -
dc.identifier.issn16625153
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3509
dc.descriptionEthanol (EtOH) research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID) exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD), we evaluated different types of basal anxiety-like responses, EtOH preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc). Additionally, we tested binge drinking by LD/HD in response to a selective OX1r antagonist following intermittent episodes of DID (iDID). We report that DID consistently segregates two neurobehavioral endophenotypes, HD vs. LD, showing differences in neophobia and/or impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC. Exposure to several intermittent episodes of EtOH DID triggered a rapid increase in EtOH intake over time in LD mice matching that observed in HD mice. Despite HD/LD endophenotypes did not show differences in EtOH intake, they still predicted the response to a pharmacological challenge with a selective OX1r antagonist. The present data underscore the relevance of HD/LD endophenotypes stemming from DID procedures for exploring neurobehavioral processes underlying the early stages of the addiction cycle and EtOH binge-drinking disorders. © 2017 Alcaraz-Iborra, Navarrete, Rodríguez-Ortega, de la Fuente, Manzanares and Cubero.
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.subjectAnxiety
dc.subjectEndophenotype
dc.subjectImpulsivity/compulsivity
dc.subjectIntermittent ethanol drinking in the dark
dc.subjectNeophobia
dc.subjectOrexin
dc.subject1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea
dc.subjectalcohol
dc.subjectmessenger RNA
dc.subjectorexin 1 receptor
dc.subjectorexin 2 receptor
dc.subjectadult
dc.subjectalcohol consumption
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectanxiety
dc.subjectArticle
dc.subjectbinge drinking
dc.subjectC57BL 6 mouse
dc.subjectconditioned place preference test
dc.subjectcontrolled study
dc.subjectelevated plus maze test
dc.subjectendophenotype
dc.subjectenzyme inhibition
dc.subjectexploratory behavior test
dc.subjectgene expression
dc.subjectimpulsiveness
dc.subjectmale
dc.subjectmouse
dc.subjectneophobia
dc.subjectnonhuman
dc.subjectnucleus accumbens
dc.subjectprefrontal cortex
dc.subjecttaste preference
dc.titleDifferent molecular/behavioral endophenotypes in C57BL/6J mice predict the impact of OX1 receptor blockade on binge-like ethanol intake
dc.typeArticle


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