| Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. | |
| | |
MedLine Citation:
|
PMID: 22569505 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Orexins (OX) and their receptors (OXR) modulate feeding, arousal, stress, and drug abuse. Neural systems that motivate and reinforce drug abuse may also underlie compulsive food seeking and intake. Therefore, the effects of GSK1059865 (5-bromo-N-[(2S,5S)-1-(3-fluoro-2-methoxybenzoyl)-5-methylpiperidin-2-yl]methyl-pyridin-2-amine), a selective OX(1)R antagonist, JNJ-10397049 (N-(2,4-dibromophenyl)-N'-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea), a selective OX(2)R antagonist, and SB-649868 (N-[((2S)-1-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}-2-piperidinyl)methyl]-1-benzofuran-4-carboxamide), a dual OX(1)/OX(2)R antagonist were evaluated in a binge eating (BE) model in female rats. BE of highly palatable food (HPF) was evoked by three cycles of food restriction followed by stress, elicited by exposing rats to HPF, but preventing them from having access to it for 15 min. Pharmacokinetic assessments of all compounds were obtained under the same experimental conditions used for the behavioral experiments. Topiramate was used as the reference compound as it selectively blocks BE in rats and humans. Dose-related thresholds for sleep-inducing effects of the OXR antagonists were measured using polysomnography in parallel experiments. SB-649868 and GSK1059865, but not JNJ-10397049, selectively reduced BE for HPF without affecting standard food pellet intake, at doses that did not induce sleep. These results indicate, for the first time, a major role of OX(1)R mechanisms in BE, suggesting that selective antagonism at OX(1)R could represent a novel pharmacological treatment for BE and possibly other eating disorders with a compulsive component. |
| | |
Authors:
|
Laura Piccoli; Maria Vittoria Micioni Di Bonaventura; Carlo Cifani; Vivian J A Costantini; Mario Massagrande; Dino Montanari; Prisca Martinelli; Marinella Antolini; Roberto Ciccocioppo; Maurizio Massi; Emilio Merlo-Pich; Romano Di Fabio; Mauro Corsi |
Related Documents
:
|
11214035 - Treatment of covert food stealing in an individual with prader-willi syndrome. 22100145 - Emas position statement: vitamin d and postmenopausal health. 20828665 - Effect of low-carbohydrate claims on consumer perceptions about food products' healthfu... 6994505 - Extremes of urine osmolality: lack of effect on red blood cell survival. 22696895 - Dietary patterns are associated with overweight and obesity in mexican school-age child... 6146445 - Camels' milk: for drinking only? |
Publication Detail:
|
Type: Journal Article Date: 2012-05-09 |
Journal Detail:
|
Title: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Volume: 37 ISSN: 1740-634X ISO Abbreviation: Neuropsychopharmacology Publication Date: 2012 Aug |
Date Detail:
|
Created Date: 2012-07-18 Completed Date: 2013-03-17 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 8904907 Medline TA: Neuropsychopharmacology Country: England |
Other Details:
|
Languages: eng Pagination: 1999-2011 Citation Subset: IM |
Affiliation:
|
GlaxoSmithKline, Medicines Research Centre, Verona, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bulimia / drug therapy, metabolism*, psychology Compulsive Behavior* / drug therapy, psychology Eating / drug effects, physiology*, psychology Female Fructose / analogs & derivatives, pharmacology, therapeutic use Intracellular Signaling Peptides and Proteins / pharmacology Male Neuropeptides / pharmacology Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled / agonists, antagonists & inhibitors, physiology* Receptors, Neuropeptide / agonists, antagonists & inhibitors, physiology* Reinforcement Schedule Sex Factors Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexin receptors; 0/orexins; 30237-26-4/Fructose; 97240-79-4/topiramate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: [Metastatic lung tumor from colon cancer with cavitation;report of a case].
Next Document: Acute stress induces selective alterations in cost/benefit decision-making.