title: Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats.
abstract: BACKGROUND
  Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF).
  
  
  OBJECTIVE
  In relation to the antistress properties of N/OFQ, we evaluated its effect on BE. After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions.
  
  
  METHODS
  In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/refeeding and then stressed, or not stressed. In the other experiments, two groups were used: rats exposed or not to food restriction.
  
  
  RESULTS
  Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream). Intracerebroventricular injections of N/OFQ of 0.5 nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions. Cycles of food restriction increased animals' sensitivity to the hyperphagic effect of N/OFQ for HPF. In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively.
  
  
  CONCLUSIONS
  These findings indicate that N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.
authors: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, MC, Italy.
authors: Maria Vittoria
authors: MV
authors: Micioni Di Bonaventura
authors: Massimo
authors: M
authors: Ubaldi
authors: Sonia
authors: S
authors: Liberati
authors: Roberto
authors: R
authors: Ciccocioppo
authors: Maurizio
authors: M
authors: Massi
authors: Carlo
authors: C
authors: Cifani
mesh_terms: D000818:Animals; D002032:Bulimia / Q000209:etiology / Q000517:prevention & control*; D031204:Caloric Restriction; D004305:Dose-Response Relationship, Drug; D005260:Female; D006963:Hyperphagia / Q000209:etiology; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy*; D017557:Ventral Tegmental Area / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat