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Orexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence

dc.contributor.authorCarvajal F.
dc.contributor.authorAlcaraz-Iborra M.
dc.contributor.authorLerma-Cabrera J.M.
dc.contributor.authorValor L.M.
dc.contributor.authorde la Fuente L.
dc.contributor.authorSanchez-Amate M.D.C.
dc.contributor.authorCubero I.
dc.date.accessioned2020-09-02T22:14:16Z
dc.date.available2020-09-02T22:14:16Z
dc.date.issued2015
dc.identifier10.1016/j.bbr.2015.03.046
dc.identifier.citation287, , 230-237
dc.identifier.issn01664328
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3938
dc.descriptionOrexins (OX) have been recently implicated in ethanol seeking and self-administration. A few recent studies have provided additional evidence that OX receptor antagonists effectively reduce voluntary ethanol consumption in subjects spontaneously showing high levels of ethanol intake. The present study further evaluates the contribution of OXR1 to excessive binge-like drinking of ethanol in ad libitum-fed C57BL/6J mice from a pharmacological and molecular approach. The main findings in the study are: (1) Icv administration of SB-334867 (3. μg/μl) blunted ethanol (20% v/v), but not saccharin (0.15% w/v) binge-like drinking in a drinking in the dark procedure, without any alteration of chow consumption or total calories ingested; (2) Icv administration of SB-334867 (3. μg/μl) increased the latency to recover the righting reflex after a sedative dose of ethanol without any significant alteration in ethanol peripheral metabolism; (3) four repetitive, 2-h daily episodes of saccharin, but not ethanol binge-like drinking blunted OXR1 mRNA expression in the lateral hypothalamus. Present findings extend the current knowledge pointing to a role for OX signaling in ethanol sedation, which might partially explain the inhibitory effect of OXR1 antagonists on ethanol consumption. Combined pharmacological and molecular data suggesting the contribution of OXR1 in ethanol binge-drinking leading us to propose the idea that targeting OXR1 could represent a novel pharmacological approach to control binge-consumption episodes of ethanol in vulnerable organisms failing to spontaneously reduce OX activity. © 2015 Elsevier B.V.
dc.language.isoen
dc.publisherElsevier
dc.subjectDrinking in the dark (DID)
dc.subjectEthanol binge-like consumption
dc.subjectEthanol sedation
dc.subjectOrexins
dc.subjectOX receptor 1
dc.subject1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea
dc.subjectalcohol
dc.subjectorexin 1 receptor
dc.subjectsaccharin
dc.subject1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
dc.subjectalcohol
dc.subjectalcohol blood level
dc.subjectbenzoxazole derivative
dc.subjectcentral depressant agent
dc.subjectdrinking water
dc.subjecthypnotic sedative agent
dc.subjectmessenger RNA
dc.subjectorexin receptor
dc.subjectorexin receptor antagonist
dc.subjectsaccharin
dc.subjecturea
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectArticle
dc.subjectbinge drinking
dc.subjectcontrolled study
dc.subjectdrinking behavior
dc.subjectdrug activity
dc.subjectfood intake
dc.subjecthomeostasis
dc.subjectlatent period
dc.subjectlateral hypothalamus
dc.subjectlocomotion
dc.subjectmale
dc.subjectmetabolism
dc.subjectmouse
dc.subjectnonhuman
dc.subjectpathogenesis
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectrepeated drug dose
dc.subjectrighting reflex
dc.subjectsedation
dc.subjectsignal transduction
dc.subjectalcohol blood level
dc.subjectanalogs and derivatives
dc.subjectanimal
dc.subjectbinge drinking
dc.subjectC57BL mouse
dc.subjectdrug effects
dc.subjectdrug therapy
dc.subjecteating
dc.subjectmetabolism
dc.subjectphysiology
dc.subjectreflex
dc.subjectAnimals
dc.subjectBenzoxazoles
dc.subjectBinge Drinking
dc.subjectBlood Alcohol Content
dc.subjectCentral Nervous System Depressants
dc.subjectDrinking Water
dc.subjectEating
dc.subjectEthanol
dc.subjectHypnotics and Sedatives
dc.subjectHypothalamic Area, Lateral
dc.subjectLocomotion
dc.subjectMale
dc.subjectMice, Inbred C57BL
dc.subjectOrexin Receptor Antagonists
dc.subjectOrexin Receptors
dc.subjectReflex
dc.subjectRNA, Messenger
dc.subjectSaccharin
dc.subjectUrea
dc.titleOrexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence
dc.typeArticle


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