Skip to main content
SpringerLink
Log in

Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals

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

Abstract

Rationale

Translational research implicates the mu opioid neurochemical system in hedonic processing, but its role in dissociable high-level cognitive functions is not well understood. Binge-eating represents a useful model of ‘behavioural addiction’ for exploring this issue.

Objective

The aim of this study was to objectively assess the cognitive effects of a mu opioid receptor antagonist in obese individuals with binge-eating symptoms.

Methods

Adults with moderate to severe binge-eating and body mass index ≥30 kg/m2 received 4 weeks of treatment with a mu opioid receptor antagonist (GSK1521498) 2 or 5 mg per day, or placebo, in a double-blind randomised parallel design. Neuropsychological assessment was undertaken at baseline and endpoint to quantify processing bias for food stimuli (visual dot probe with 500- and 2,000-ms stimulus presentations and food Stroop tasks) and other distinct cognitive functions (N-back working memory, sustained attention, and power of attention tasks).

Results

GSK1521498 5 mg/day significantly reduced attentional bias for food cues on the visual dot probe task versus placebo (p = 0.042), with no effects detected on other cognitive tasks (all p > 0.10). The effect on attentional bias was limited to the longer stimulus duration condition in the higher dose cohort alone.

Conclusions

These findings support a central role for mu opioid receptors in aspects of attentional processing of food cues but militate against the notion of major modulatory influences of mu opioid receptors in working memory and sustained attention. The findings have implications for novel therapeutic directions and suggest that the role of different opioid receptors in cognition merits further research.

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

Similar content being viewed by others

References

  • Anton RF, Drobes DJ et al (2004) Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking. Psychopharmacology (Berl) 173(1–2):32–40

    Article  CAS  Google Scholar 

  • Anton RF, O’Malley SS et al (2006) Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295(17):2003–2017

    Article  PubMed  CAS  Google Scholar 

  • Apfelbaum M, Mandenoff A (1981) Naltrexone suppresses hyperphagia induced in the rat by a highly palatable diet. Pharmacol Biochem Behav 15(1):89–91

    Article  PubMed  CAS  Google Scholar 

  • Asad N, Karmaliani R et al (2010) Prevalence of suicidal thoughts and attempts among pregnant Pakistani women. Acta Obstet Gynecol Scand 89(12):1545–1551

    Article  PubMed  Google Scholar 

  • Avena NM, Bocarsly ME et al (2011) Overlaps in the nosology of substance abuse and overeating: the translational implications of “food addiction”. Curr Drug Abuse Rev 4(3):133–139

    Article  PubMed  Google Scholar 

  • Beck AT, Beamesderfer A (1974) Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatr 7:151–169

    CAS  Google Scholar 

  • Beck AT, Ward CH et al (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Article  PubMed  CAS  Google Scholar 

  • Bello NT, Patinkin ZW et al (2011) Opioidergic consequences of dietary-induced binge eating. Physiol Behav 104(1):98–104

    Article  PubMed  CAS  Google Scholar 

  • Bencherif B, Guarda AS et al (2005) Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. J Nucl Med 46(8):1349–1351

    PubMed  CAS  Google Scholar 

  • Berrendero F, Robledo P et al (2010) Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system. Neurosci Biobehav Rev 35(2):220–231

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC (2009) ‘Liking’ and ‘wanting’ food rewards: brain substrates and roles in eating disorders. Physiol Behav 97(5):537–550

    Article  PubMed  CAS  Google Scholar 

  • Brignell C, Griffiths T et al (2009) Attentional and approach biases for pictorial food cues. Influence of external eating. Appetite 52(2):299–306

    Article  PubMed  Google Scholar 

  • Calitri R, Pothos EM et al (2010) Cognitive biases to healthy and unhealthy food words predict change in BMI. Obesity (Silver Spring) 18(12):2282–2287

    Article  Google Scholar 

  • Callicott JH, Ramsey NF et al (1998) Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia. Neuropsychopharmacology 18(3):186–196

    Article  PubMed  CAS  Google Scholar 

  • Chamberlain SR, Sahakian BJ (2007) The neuropsychiatry of impulsivity. Curr Opin Psychiatry 20(3):255–261

    PubMed  Google Scholar 

  • Chamberlain, SR, Robbins TW et al (2010) Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biol Psychiatry

  • Cohen RM, Cohen MR et al (1983) High-dose naloxone affects task performance in normal subjects. Psychiatry Res 8(2):127–136

    Article  PubMed  CAS  Google Scholar 

  • Colantuoni C, Schwenker J, McCarthy J et al (2001) Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport 12:3549–3552

    Google Scholar 

  • Corwin RL, Avena NM et al (2011) Feeding and reward: perspectives from three rat models of binge eating. Physiol Behav 104(1):87–97

    Article  PubMed  CAS  Google Scholar 

  • Cox WM, Fadardi JS et al (2006) The addiction-stroop test: theoretical considerations and procedural recommendations. Psychol Bull 132(3):443–476

    Article  PubMed  Google Scholar 

  • Davis C, Carter JC (2009) Compulsive overeating as an addiction disorder. a review of theory and evidence. Appetite 53(1):1–8

    Article  PubMed  Google Scholar 

  • Davis C, Zai C et al (2011) Opiates, overeating and obesity: a psychogenetic analysis. Int J Obes (Lond) 35(10):1347–1354

    Article  CAS  Google Scholar 

  • Evans RG, Ludbrook J (1990) Effects of mu-opioid receptor agonists on circulatory responses to simulated haemorrhage in conscious rabbits. Br J Pharmacol 100(3):421–426

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Serrano MJ, Perez-Garcia M et al (2011) What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance? Neurosci Biobehav Rev 35(3):377–406

    Article  PubMed  CAS  Google Scholar 

  • Fulton S (2010) Appetite and reward. Front Neuroendocrinol 31(1):85–103

    Article  PubMed  Google Scholar 

  • Giuliano C, Robbins TW, Nathan PJ, Bullmore ET, Everitt BJ (2012) Inhibition of opioid transmission at the μ-opioid receptor prevents both food seeking and binge-like eating. Neuropsychopharmacol (in press)

  • Gladis MM, Wadden TA et al (1998) A comparison of two approaches to the assessment of binge eating in obesity. Int J Eat Disord 23(1):17–26

    Article  PubMed  CAS  Google Scholar 

  • Goodman A (2008) Neurobiology of addiction. An integrative review. Biochem Pharmacol 75(1):266–322

    Article  PubMed  CAS  Google Scholar 

  • Gormally J, Black S et al (1982) The assessment of binge eating severity among obese persons. Addict Behav 7(1):47–55

    Article  PubMed  CAS  Google Scholar 

  • Grant JE, Brewer JA et al (2006) The neurobiology of substance and behavioral addictions. CNS Spectr 11(12):924–930

    PubMed  Google Scholar 

  • Gruber SA, Silveri MM et al (2007) Neuropsychological consequences of opiate use. Neuropsychol Rev 17(3):299–315

    Article  PubMed  Google Scholar 

  • Hatsukami DK, Mitchell JE et al (1986) Effect of naltrexone on mood and cognitive functioning among overweight men. Biol Psychiatry 21(3):293–300

    Article  PubMed  CAS  Google Scholar 

  • Hepworth R, Mogg K et al (2010) Negative mood increases selective attention to food cues and subjective appetite. Appetite 54(1):134–142

    Article  PubMed  Google Scholar 

  • Itoh J, Ukai M et al (1994) Dynorphin A-(1-13) potently improves the impairment of spontaneous alternation performance induced by the mu-selective opioid receptor agonist DAMGO in mice. J Pharmacol Exp Ther 269(1):15–21

    PubMed  CAS  Google Scholar 

  • Jacobs-Pilipski MJ, Wilfley DE et al (2007) Placebo response in binge eating disorder. Int J Eat Disord 40(3):204–211

    Article  PubMed  Google Scholar 

  • Jang CG, Lee SY et al (2003) Impaired water maze learning performance in mu-opioid receptor knockout mice. Brain Res Mol Brain Res 117(1):68–72

    Article  PubMed  CAS  Google Scholar 

  • Kennedy DO, Scholey AB et al (2000) The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl) 151(4):416–423

    Article  CAS  Google Scholar 

  • Le Merrer J, Becker JA et al (2009) Reward processing by the opioid system in the brain. Physiol Rev 89(4):1379–1412

    Article  PubMed  Google Scholar 

  • Leventhal L, Kirkham TC et al (1995) Selective actions of central mu and kappa opioid antagonists upon sucrose intake in sham-fed rats. Brain Res 685(1–2):205–210

    Article  PubMed  CAS  Google Scholar 

  • Marks-Kaufman R, Kanarek RB (1981) Modifications of nutrient selection induced by naloxone in rats. Psychopharmacology (Berl) 74(4):321–324

    Article  CAS  Google Scholar 

  • Martin del Campo AF, McMurray RG et al (1992) Effect of 12-hour infusion of naloxone on mood and cognition in normal male volunteers. Biol Psychiatry 32(4):344–353

    Article  PubMed  CAS  Google Scholar 

  • McClure CK, Patrick TE et al (2011) Birth outcomes following self-inflicted poisoning during pregnancy, California, 2000 to 2004. J Obstet Gynecol Neonatal Nurs 40(3):292–301

    Article  PubMed  Google Scholar 

  • Milner A, McClure R et al (2011) Globalisation and suicide: an empirical investigation in 35 countries over the period 1980–2006. Health Place 17(4):996–1003

    Article  PubMed  Google Scholar 

  • Milner A, McClure R et al (2012) Socio-economic determinants of suicide: an ecological analysis of 35 countries. Soc Psychiatry Psychiatr Epidemiol 47(1):19–27

    Article  PubMed  Google Scholar 

  • Mitchell JE, Laine DE et al (1986) Naloxone but not CCK-8 may attenuate binge-eating behavior in patients with the bulimia syndrome. Biol Psychiatry 21(14):1399–1406

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JE, Morley JE et al (1987) High-dose naltrexone therapy and dietary counseling for obesity. Biol Psychiatry 22(1):35–42

    Article  PubMed  CAS  Google Scholar 

  • Napolitano A, Miller SR et al (2012) Prediction of weight loss and weight regain following dietary, lifestyle and pharmacological intervention. Clin Pharmacol Ther 91(6):1027–1034

    Article  PubMed  CAS  Google Scholar 

  • Nathan PJ, Bullmore ET (2009) From taste hedonics to motivational drive: central mu-opioid receptors and binge-eating behaviour. Int J Neuropsychopharmacol 12(7):995–1008

    Article  PubMed  CAS  Google Scholar 

  • Nathan PJ et al (2011a) Multiple-dose safety, pharmacokinetics and pharmacodynamics of the mu-opioid receptor inverse agonist GSK1521498. J Clin Pharmacol. doi:10.1177/0091270011421785

  • Nathan PJ, O’Neill BV et al (2011b) Opioid receptor modulation of hedonic taste preference and food intake: a single-dose safety, pharmacokinetic, and pharmacodynamic investigation with GSK1521498, a novel μ-opioid receptor inverse agonist. J Clin Pharmacol 52(4):464–474

    PubMed  Google Scholar 

  • Nathan PJ, O’Neill BV et al (2011c) The effects of the dopamine D3 receptor antagonist GSK598809 on attentional bias to palatable food cues in overweight and obese subjects. Int J Neuropsychopharmacol 1–13

  • Quednow BB, Csomor PA et al (2008) Sensorimotor gating and attentional set-shifting are improved by the mu-opioid receptor agonist morphine in healthy human volunteers. Int J Neuropsychopharmacol 11(5):655–669

    Article  PubMed  CAS  Google Scholar 

  • Rabiner EA, Beaver J et al (2011) Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans. Mol Psychiatry 16(8):826–835, 785

    Article  PubMed  CAS  Google Scholar 

  • Riba J, Rodriguez-Fornells A et al (2005) Noradrenergic stimulation enhances human action monitoring. J Neurosci 25(17):4370–4374

    Article  PubMed  CAS  Google Scholar 

  • Robbins TW, Arnsten AF (2009) The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci 32:267–287

    Article  PubMed  CAS  Google Scholar 

  • Rosner S, Hackl-Herrwerth A et al (2010) Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev (12):CD001867

  • Sanger DJ, McCarthy PS (1981) Increased food and water intake produced in rats by opiate receptor agonists. Psychopharmacology (Berl) 74(3):217–220

    Article  CAS  Google Scholar 

  • Shah J, Wesnes KA et al (2006) Effects of food on the single-dose pharmacokinetics/pharmacodynamics of tizanidine capsules and tablets in healthy volunteers. Clin Ther 28(9):1308–1317

    Article  PubMed  CAS  Google Scholar 

  • Spiegel TA, Stunkard AJ et al (1987) Effect of naltrexone on food intake, hunger, and satiety in obese men. Physiol Behav 40(2):135–141

    Article  PubMed  CAS  Google Scholar 

  • Striegel-Moore RH, Cachelin FM et al (2001) Comparison of binge eating disorder and bulimia nervosa in a community sample. Int J Eat Disord 29(2):157–165

    Article  PubMed  CAS  Google Scholar 

  • Stunkard A (1990) A description of eating disorders in 1932. Am J Psychiatry 147(3):263–268

    PubMed  CAS  Google Scholar 

  • Stunkard AJ, Wadden TA (1992) Psychological aspects of severe obesity. Am J Clin Nutr 55(2 Suppl):524S–532S

    PubMed  CAS  Google Scholar 

  • Swanson SA, Crow SJ et al (2011) Prevalence and correlates of eating disorders in adolescents: results from the national comorbidity survey replication adolescent supplement. Arch Gen Psychiatry 68(7):714–723

    Article  PubMed  Google Scholar 

  • Ukai M, Watanabe Y et al (2000) Effects of endomorphins-1 and -2, endogenous mu-opioid receptor agonists, on spontaneous alternation performance in mice. Eur J Pharmacol 395(3):211–215

    Article  PubMed  CAS  Google Scholar 

  • Wagner JJ, Terman GW et al (1993) Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature 363(6428):451–454

    Article  PubMed  CAS  Google Scholar 

  • Will MJ, Franzblau EB et al (2003) Nucleus accumbens mu-opioids regulate intake of a high-fat diet via activation of a distributed brain network. J Neurosci 23(7):2882–2888

    PubMed  CAS  Google Scholar 

  • Xie CW, Morrisett RA et al (1992) Mu opioid receptor-mediated modulation of synaptic currents in dentate granule cells of rat hippocampus. J Neurophysiol 68(4):1113–1120

    PubMed  CAS  Google Scholar 

  • Yeomans MR, Gray RW (2002) Opioid peptides and the control of human ingestive behaviour. Neurosci Biobehav Rev 26(6):713–728

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all participants and support staff at GSK. This study was funded and conducted by GSK. SRC is an NIHR Academic Clinical Fellow in Psychiatry; he received no financial compensation from GSK for work on this project. SRC consults for Cambridge Cognition, Shire, Lilly, and P1Vital. KM and BB’s primary employer is the University of Southampton, and these authors received compensation from GSK for work on this project. The following authors are employees of GSK and have shares in the company: CD, WT, KM, BS, AN, DR, EB and PN.

Author information

Authors and Affiliations

  1. Clinical Unit Cambridge, GlaxoSmithKline, Addenbrooke’s Hospital, Cambridge, CB0 0QQ, UK

    Samuel R. Chamberlain, Annelize Koch, Chris M. Dodds, Wenli X. Tao, Kay Maltby, Bhopinder Sarai, Antonella Napolitano, Duncan B. Richards, Edward T. Bullmore & Pradeep J. Nathan

  2. Department of Psychiatry, Level E4, Addenbrooke’s Hospital, University of Cambridge, Cambridge, CB0 0QQ, UK

    Samuel R. Chamberlain, Edward T. Bullmore & Pradeep J. Nathan

  3. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK

    Samuel R. Chamberlain & Edward T. Bullmore

  4. Department of Psychology, University of Southampton, Southampton, UK

    Karin Mogg & Brendan P. Bradley

Authors
  1. Samuel R. Chamberlain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karin Mogg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brendan P. Bradley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annelize Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chris M. Dodds
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenli X. Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kay Maltby
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bhopinder Sarai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Antonella Napolitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Duncan B. Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Edward T. Bullmore
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pradeep J. Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Samuel R. Chamberlain or Pradeep J. Nathan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chamberlain, S.R., Mogg, K., Bradley, B.P. et al. Effects of mu opioid receptor antagonism on cognition in obese binge-eating individuals. Psychopharmacology 224, 501–509 (2012). https://doi.org/10.1007/s00213-012-2778-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-012-2778-x

Keywords

Search

Navigation