title: Orexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence.
abstract: Orexins (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.
authors.affiliation: Carrera de Psicología, Facultad Ciencias Jurídicas y Sociales, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería 04120, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Alcaraz-Iborra
authors.affiliation: Carrera de Psicología, Facultad Ciencias Jurídicas y Sociales, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.affiliation: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Alicante 03550, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Valor
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería 04120, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: de la Fuente
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería 04120, Spain.
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Sanchez-Amate
authors.affiliation: Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, Almería 04120, Spain; Carrera de Psicología, Facultad Ciencias Jurídicas y Sociales, Universidad Autónoma de Chile, Santiago de Chile, Chile. Electronic address: icubero@ual.es.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cubero
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D063425:Binge Drinking / Q000188:drug therapy* / Q000378:metabolism*; D000067401:Blood Alcohol Content; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D060766:Drinking Water / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012439:Saccharin / Q000008:administration & dosage; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D000067401:Blood Alcohol Content; D002492:Central Nervous System Depressants; D060766:Drinking Water; D006993:Hypnotics and Sedatives; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D012333:RNA, Messenger; D000431:Ethanol; D014508:Urea; D012439:Saccharin
keywords: Drinking in the dark (DID); Ethanol binge-like consumption; Ethanol sedation; OX receptor 1; Orexins