title: Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.
abstract: We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders.
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, I-62032 Camerino, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Micioni Di Bonaventura
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, I-62032 Camerino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, I-00185 Rome, Italy, and.
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.affiliation: Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224.
authors.forename: Jennifer M
authors.identifier: http://orcid.org/0000-0001-5636-4071
authors.initials: JM
authors.lastname: Bossert
authors.affiliation: Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224.
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, I-62032 Camerino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.affiliation: Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224.
authors.forename: Robyn
authors.identifier: http://orcid.org/0000-0002-3557-6056
authors.initials: R
authors.lastname: St Laurent
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, I-00185 Rome, Italy, and.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, I-62032 Camerino, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
authors.affiliation: Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, I-62032 Camerino, Italy, Intramural Research Program, National Institutes of Health/National Institute on Drug Abuse, Baltimore, Maryland 21224 carlo.cifani@unicam.it carlo.cifani@nih.gov.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
mesh_terms: D000818:Animals; D002032:Bulimia / Q000209:etiology*; D003259:Consummatory Behavior / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005508:Food Deprivation; D007276:Injections, Intraventricular; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications*; D013997:Time Factors
chemical_list: D016761:Oncogene Proteins v-fos; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; C113202:phenylalanyl corticotropin-releasing factor (12-41); D003346:Corticotropin-Releasing Hormone
keywords: BNST; CRF1 receptor antagonist; R121919; binge eating; palatable food; stress and food restriction