Skip to main content
SpringerLink
Log in

Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

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).

Objectives

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.

Materials and 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • American Psychiatric Association (2000) Diagnostic and statistic manual of mental disorders, IV-TR. APA, Washington

    Google Scholar 

  • Arbaizar B, Gómez-Acebo I, Llorca J (2008) Efficacy of topiramate in bulimia nervosa and binge-eating disorder: a systematic review. Gen Hosp Psychiatry 30:471–475

    Article  PubMed  Google Scholar 

  • Avena N, Rada P, Hoebel B (2006) Sugar bingeing in rats. Current protocols in neuroscience. Unit 9.23C. Wiley, Indianapolis

    Google Scholar 

  • Avena NM, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32:20–39

    Article  PubMed  CAS  Google Scholar 

  • Broft AI, Spanos A, Corwin RL, Mayer L, Steinglass J, Devlin MJ, Attia E, Walsh BT (2007) Baclofen for binge eating: an open-label trial. Int J Eat Disord 40:687–691

    Article  PubMed  Google Scholar 

  • Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, Grandy DK (1994) Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. FEBS Lett 347:284–288

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Panocka I, Polidori C, Regoli D, Massi M (1999) Effect of nociceptin on alcohol intake in alcohol-preferring rats. Psychopharmacology (Berl) 141:220–224

    Article  CAS  Google Scholar 

  • Ciccocioppo R, Angeletti S, Panocka I, Massi M (2000) Nociceptin/orphanin FQ and drugs of abuse. Peptides 21:1071–1080

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Martin-Fardon R, Weiss F, Massi M (2001) Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats. Neuroreport 12:1145–1149

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Biondini M, Antonelli L, Wichmann J, Jenck F, Massi M (2002) Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198. Psychopharmacology 161:113–119

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Economidou D, Fedeli A, Massi M (2003a) The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats. Physiol Behav 79:121–128

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Fedeli A, Economidou D, Policani F, Weiss F, Massi M (2003b) The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ. J Neurosci 23:9445–9451

    PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Cippitelli A, Economidou D, Fedeli A, Massi M (2004a) Nociceptin/orphanin FQ acts as a functional antagonist of corticotropin-releasing factor to inhibit its anorectic effect. Physiol Behav 82:63–68

    Article  PubMed  CAS  Google Scholar 

  • Ciccocioppo R, Economidou D, Fedeli A, Angeletti S, Weiss F, Heilig M, Massi M (2004b) Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats. Psychopharmacology 172:170–178

    Article  PubMed  CAS  Google Scholar 

  • Cifani C, Polidori C, Melotto S, Ciccocioppo R, Massi M (2009) A preclinical model of binge-eating elicited by yo-yo dieting and stressful exposure to food: effect of sibutramine, fluoxetine, topiramate and midazolam. Psychopharmacology 204:113–125

    Article  PubMed  CAS  Google Scholar 

  • Cifani C, Micioni Di Bonaventura MV, Vitale G, Ruggieri V, Ciccocioppo R, Massi M (2010) Effect of salidroside, active principle of Rhodiola rosea extract, on binge eating. Physiol Behav 101:555–562

    Article  PubMed  CAS  Google Scholar 

  • Corwin RL, Wojnicki FH (2006) Binge eating in rats with limited access to vegetable shortening. Current protocols in neuroscience: unit 9.23B. Wiley, Indianapolis

    Google Scholar 

  • Corwin RL, Avena NM, Boggiano MM (2011) Feeling and reward: perspective from three rat models of binge eating. Physiol Behav 104:87–97

    Article  PubMed  CAS  Google Scholar 

  • Cottone P, Sabino V, Roberto M, Bajo M, Pockros L, Frihauf JB, Fekete EM, Steardo L, Rice KC, Grigoriadis DE, Conti B, Koob GF, Zorrilla EP (2009) CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci 106:20016–20020

    PubMed  CAS  Google Scholar 

  • Dallman MF, Pecoraro NC, la Fleur SE (2005) Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun 19:275–280

    Article  PubMed  Google Scholar 

  • Economidou D, Policani F, Angellotti T, Massi M, Terada T, Ciccocioppo R (2006) Effect of novel NOP receptor ligands on food intake in rats. Peptides 27:775–783

    Article  PubMed  CAS  Google Scholar 

  • Freeman LM, Gil KM (2004) Daily stress, coping, and dietary restraint in binge eating. Int J Eat Disord 36:204–212

    Article  PubMed  Google Scholar 

  • Gavioli EC, Calò G (2006) Antidepressant- and anxiolytic-like effects of nociceptin/orphanin FQ receptor ligands. Naunyn Schmiedebergs Arch Pharmacol 372:319–330

    Article  PubMed  CAS  Google Scholar 

  • Gearhardt AN, Corbin WR, Brownell KD (2011a) Food addiction: an examination of the diagnostic criteria for dependence. J Addict Med 3:1–7

    Article  Google Scholar 

  • Gearhardt AN, Yokum S, Orr PT, Stice E, Corbin WR, Brownell KD (2011b) Neural correlates of food addiction. Arch Gen Psychiatry 68:808–816

    Article  PubMed  Google Scholar 

  • Gold MS, Frost-Pineda K, Jacobs WS (2003) Overeating, binge eating, and eating disorders as addictions. Psychiatr Ann 33:112–116

    Google Scholar 

  • Haas DA, George SR (1988) Single or repeated mild stress increases synthesis and release of hypothalamic corticotropin-releasing factor. Brain Res 461:230–237

    Article  PubMed  CAS  Google Scholar 

  • Hagan MM, Wauford PK, Chandler PC, Jarrett LA, Rybak RJ, Blackburn K (2002) A new animal model of binge-eating: key synergistic role of past caloric restriction and stress. Physiol Behav 77:45–54

    Article  PubMed  CAS  Google Scholar 

  • Hoebel BG (1985) Brain neurotransmitters in food and drug reward. Am J Clin Nutr 42(Suppl 5):1133–1150

    PubMed  CAS  Google Scholar 

  • Hudson JI, Hiripi E, Pope HG Jr, Kessler RC (2007) The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 61:348–358

    Article  PubMed  Google Scholar 

  • Hurd YL, Herkenham M (1993) Molecular alterations in the neostriatum of human cocaine addicts. Synapse 13:357–369

    Article  PubMed  CAS  Google Scholar 

  • Ifland JR, Preuss HG, Marcus MT, Rourke KM, Taylor WC, Burau K et al (2009) Refined food addiction: a classic substance use disorder. Med Hypotheses 72:518–526

    Article  PubMed  CAS  Google Scholar 

  • Jenck F, Moreau JL, Martin JR, Kilpatrick GJ, Reinscheid RK, Monsma FJ Jr, Nothacker HP, Civelli O (1997) Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress. Proc Natl Acad Sci USA 94:14854–14858

    Article  PubMed  CAS  Google Scholar 

  • Jenck F, Wichmann J, Dautzenberg FM, Moreau JL, Ouagazzal AM, Martin JR, Lundstrom K, Cesura AM, Poli SM, Roever S, Kolczewski S, Adam G, Kilpatrick G (2000) A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat. Proc Natl Acad Sci USA 97:4938–4943

    Article  PubMed  CAS  Google Scholar 

  • Johnson PM, Kenny PJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci 13:635–641

    Article  PubMed  CAS  Google Scholar 

  • King BM (2006) The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav 87:221–244

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11–34

    Article  PubMed  CAS  Google Scholar 

  • Koster A, Montkowski A, Schulz S, Stube EM, Knaudt K, Jenck F, Moreau JL, Nothacker HP, Civelli O, Reinscheid RK (1999) Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice. Proc Natl Acad Sci USA 96:10444–10449

    Article  PubMed  CAS  Google Scholar 

  • Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535

    Article  PubMed  CAS  Google Scholar 

  • Meyer F (2008) Alleviation of both binge eating and sexual dysfunction with naltrexone. J Clin Psychopharmacol 28:722–723

    Article  PubMed  Google Scholar 

  • Micioni Di B MV, Cifani C, Rice KC, Ciccocioppo R, Massi M (2011) Effect of the CRF-1 receptor antagonist R121919 on binge eating. 19th Annual Meeting of the Society for the Study of Ingestive Behavior. Appetite 57S:S1–S49

  • Micioni Di Bonaventura MV, Vitale G, Massi M, Cifani C (2012a) Effect of Hypericum perforatum extract in an experimental model of binge eating in female rats. J Obes 2012:956137

  • Micioni Di Bonaventura MV, Cifani C, Lambertucci C, Volpini R, Cristalli G, Massi M (2012b) A(2A) adenosine receptor agonists reduce both high-palatability and low-palatability food intake in female rats. Behav Pharmacol 5–6:567–574

    Article  Google Scholar 

  • Mollereau C, Mouledous L (2000) Tissue distribution of the opioid receptor-like (ORL1) receptor. Peptides 21:907–917

    Article  PubMed  CAS  Google Scholar 

  • Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (1994) ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett 341:33–38

    Article  PubMed  CAS  Google Scholar 

  • National Institute for Clinical Excellence (2004) Eating disorders—core interventions in the treatment and management of anorexia nervosa, bulimia nervosa, and related eating disorders. NICE clinical guideline no 9. NICE, London

    Google Scholar 

  • Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Watson SJ Jr (1999) Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat. J Comp Neurol 406:503–547

    Article  PubMed  CAS  Google Scholar 

  • Neal CR Jr, Akil H, Watson SJ Jr (2001) Expression of orphanin FQ and the opioid receptor-like (ORL1) receptor in the developing human and rat brain. J Chem Neuroanat 22:219–249

    Article  PubMed  CAS  Google Scholar 

  • Pankevich DE, Teegarden SL, Hedin AD, Jensen CL, Bale TL (2010) Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating. J Neurosci 30:16399–16407

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, San Diego

    Google Scholar 

  • Pelchat ML, Johnson A, Chan R, Valdez J, Ragland JD (2004) Images of desire: food-craving activation during fMRI. Neuroimagen 23:1486–1493

    Article  Google Scholar 

  • Piccoli L, Micioni Di Bonaventura MV, Cifani C, Costantini VJ, Massagrande M, Montanari D, Martinelli P, Antolini M, Ciccocioppo R, Massi M, Merlo-Pich E, Di Fabio R, Corsi M (2012) Role of orexin-1 receptor mechanisms on compulsive food consumption in a model of binge eating in female rats. Neuropsychopharmacology 37:1999–2011

    Article  PubMed  CAS  Google Scholar 

  • Polidori C, de Caro G, Massi M (2000) The hyperphagic effect of nociceptin/orphanin FQ in rats. Peptides 21:1051–1062

    Article  PubMed  CAS  Google Scholar 

  • Polivy J, Zeitlin SB, Herman CP, Beal AL (1994) Food restriction and binge eating: a study of former prisoner of war. J Abnorm Psychol 103:409–411

    Article  PubMed  CAS  Google Scholar 

  • Pomonis JD, Billington CJ, Levine AS (1996) Orphanin FQ, agonist of orphan opioid receptor ORL1, stimulates feeding in rats. Neuroreport 8:369–371

    Article  PubMed  CAS  Google Scholar 

  • Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ Jr, Civelli O (1995) Orphanin FQ: a neuropeptide that activates an opioid-like G protein-coupled receptor. Science 270:792–794

    Article  PubMed  CAS  Google Scholar 

  • Rodi D, Zucchini S, Simonato M, Cifani C, Massi M, Polidori C (2008) Functional antagonism between nociceptin/orphanin FQ N/OFQ and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis. Psychopharmacology 196:523–531

    Article  PubMed  CAS  Google Scholar 

  • Schulz S, Schreff M, Nuss D, Gramsch C, Hollt V (1996) Nociceptin/orphanin FQ and opioid peptides show overlapping distribution but not co-localization in pain-modulatory brain regions. Neuroreport 7:3021–3025

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Erb S, Stewart J (2000) Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res Brain Res Rev 33:13–33

    Article  PubMed  CAS  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359

    Article  PubMed  CAS  Google Scholar 

  • Stratford TR, Holahan MR, Kelley AE (1997) Injections of nociceptin into nucleus accumbens shell or ventromedial hypothalamic nucleus increase food intake. Neuroreport 8:423–426

    Article  PubMed  CAS  Google Scholar 

  • Teegarden SL, Bale TL (2008) Effects of stress on dietary preference and intake are dependent on access and stress sensitivity. Physiol Behav 93:713–723

    Article  PubMed  CAS  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397

    Article  PubMed  CAS  Google Scholar 

  • Varty GB, Hyde LA, Hodgson RA, Lu SX, McCool MF, Kazdoba TM, Del Vecchio RA, Guthrie DH, Pond AJ, Grzelak ME, Xu X, Korfmacher WA, Tulshian D, Parker EM, Higgins GA (2005) Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species. Psychopharmacology 182:132–143

    Article  PubMed  CAS  Google Scholar 

  • Vitale G, Arletti R, Ruggieri V, Cifani C, Massi M (2006) Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats. Peptides 27:2193–2200

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–560

    Article  PubMed  CAS  Google Scholar 

  • Wang B, Shaham Y, Zitzman D, Azari S, Wise RA, You ZB (2005) Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking. J Neurosci 25:5389–5396

    Article  PubMed  CAS  Google Scholar 

  • Wang GJ, Geliebter A, Volkow ND, Telang FW, Logan J, Jayne MC, Galanti K et al (2011) Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity 19:1601–1608

    Article  PubMed  CAS  Google Scholar 

  • Wardle J, Steptoe A, Oliver G, Lipsey Z (2000) Stress, dietary restraint and food intake. J Psychosom Res 48:195–202

    Article  PubMed  CAS  Google Scholar 

  • Waters A, Hill A, Waller G (2001) Internal and external antecedents of binge eating episodes in a group of women with bulimia nervosa. Int J Eat Disord 29:17–22

    Article  PubMed  CAS  Google Scholar 

  • Wing RR, Phelan S (2005) Long-term weight loss maintenance. Am J Clin Nutr 82:222S–225S

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Dr. Remo Guerrini, University of Ferrara, for the gift of N/OFQ and Dr. Charles L. Pickens (NIAAA/NIH) for stylistic correction of the manuscript.

Author information

Authors and Affiliations

  1. School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, 62032, Camerino, MC, Italy

    Maria Vittoria Micioni Di Bonaventura, Massimo Ubaldi, Sonia Liberati, Roberto Ciccocioppo, Maurizio Massi & Carlo Cifani

Authors
  1. Maria Vittoria Micioni Di Bonaventura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimo Ubaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sonia Liberati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberto Ciccocioppo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maurizio Massi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carlo Cifani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlo Cifani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Micioni Di Bonaventura, M.V., Ubaldi, M., Liberati, S. et al. Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats. Psychopharmacology 228, 53–63 (2013). https://doi.org/10.1007/s00213-013-3013-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3013-0

Keywords

Search

Navigation