title: Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating.
abstract: Binge eating is a dysregulated form of feeding behavior that occurs in multiple eating disorders including binge-eating disorder, the most common eating disorder. Feeding is a complex behavioral program supported through the function of multiple brain regions and influenced by a diverse array of receptor signaling pathways. Previous studies have shown the overexpression of the opioid neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role of endogenous nociceptin receptor (NOP) in naturally occurring palatability-induced hyperphagia is unknown. In this study we adapted a simple, replicable form of binge eating of high fat food (HFD). We found that male and female C57BL/6J mice provided with daily one-hour access sessions to HFD eat significantly more during this period than those provided with continuous 24h access. This form of feeding is rapid and entrained. Chronic intermittent HFD binge eating produced hyperactivity and increased light zone exploration in the open field and light-dark assays respectively. Treatment with the potent and selective NOP antagonist SB 612111 resulted in a significant dose-dependent reduction in binge intake in both male and female mice, and, unlike treatment with the serotonin selective reuptake inhibitor fluoxetine, produced no change in total 24-h food intake. SB 612111 treatment also significantly decreased non-binge-like acute HFD consumption in male mice. These data are consistent with the hypothesis that high fat binge eating is modulated by NOP signaling and that the NOP system may represent a promising novel receptor to explore for the treatment of binge eating.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Hardaway
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jensen
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kim
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Mazzone
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Sugam
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Diberto
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Lowery-Gionta
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Hwa
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pleil
authors.affiliation: UNC Department of Psychiatry, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Nutrition, University of North Carolina at Chapel Hill, NC, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA; UNC Department of Pharmacology, University of North Carolina at Chapel Hill, NC, USA. Electronic address: thomas_kash@med.unc.edu.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D002032:Bulimia / Q000188:drug therapy* / Q000209:etiology*; D003508:Cycloheptanes / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000627:therapeutic use*; D011957:Receptors, Opioid / Q000378:metabolism; D012727:Sex Characteristics; D013997:Time Factors; D000094942:Nociceptin Receptor
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003508:Cycloheptanes; D010880:Piperidines; D011957:Receptors, Opioid; C482404:cis-1-methyl-7-((4-(2,6-dichlorophenyl)piperidin-1-yl)methyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol; D005473:Fluoxetine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse
keywords: Binge eating; Fluoxetine; High fat; Hyperphagia; Intermittent access; Nociceptin