title: Binge-like consumption of caloric and non-caloric palatable substances in ad libitum-fed C57BL/6J mice: pharmacological and molecular evidence of orexin involvement.
abstract: The orexin (OX) system has been implicated in food-reinforced behavior, food-seeking and food overconsumption. Recent evidence suggests that OX signaling might influence consumption of palatable foods with high reinforcing value depending upon the caloric status of the animal. The present study evaluates from a pharmacological and a molecular approach the contribution of OX to excessive binge-like consumption of highly preferred palatable substances (sucrose and saccharin) in ad libitum-fed C57BL/6J mice. The main findings of this study are: (1) intraperitoneal (ip) injection of SB-334867 (10, 20 or 30mg/kg), a selective OXR1 antagonist, significantly decreased binge-like consumption of sucrose (10%, w/v) and saccharin (0.15%, w/v) during the test day in a Drinking in the Dark procedure in ad libitum-fed animals, without evidence of any significant alteration of locomotor activity. (2) Four repetitive, 2-h daily episodes of sucrose and saccharin (but not water) binge-like drinking significantly dampened OX mRNA expression in the LH. Present findings show for the first time a role for OXR1 signaling in binge-like consumption of palatable substances in animals under no caloric needs. Targeting OXR1 could represent a novel pharmacological approach to treat binge-eating episodes.
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: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.affiliation: Carrera de Psicología, Facultad Ciencias Jurídicas y Sociales, Universidad Autónoma de Chile, Santiago de Chile, Chile.
authors.forename: José 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; 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; D002032:Bulimia; D019422:Dietary Sucrose / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology*; D060766:Drinking Water / Q000008:administration & dosage; D002149:Energy Intake / Q000187:drug effects* / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009287:Naphthyridines; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000068797:Orexins; D012333:RNA, Messenger / Q000378:metabolism; 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; D019422:Dietary Sucrose; D060766:Drinking Water; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009687:Nuclear Proteins; D000068797:Orexins; C423572:Oxr1 protein, mouse; D012333:RNA, Messenger; D014508:Urea; D012439:Saccharin
keywords: Binge-like consumption; Drinking in the Dark (DID); Orexins; Palatable substances