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Reversible suppression of food reward behavior by chronic mu-opioid receptor antagonism in the nucleus accumbens
Open accessAbstract
Overindulgence in easily available energy-dense palatable foods is thought to be an important factor in the current obesity epidemic but the underlying neural mechanisms are not well understood. Here we demonstrate that mu-opioid receptor signaling in the nucleus accumbens may be important. Protracted suppression of endogenous mu-opioid receptor signaling focused on the nucleus accumbens shell for several days by means of microinjected beta-funaltrexamine (BFNA) diminished both "liking" of sucrose, as indicated by fewer positive hedonic orofacial responses, and the incentive reinforcement value ("wanting") of a food reward, as indicated by lower completion speed and increased time being distracted in the incentive runway. BFNA-treatment also decreased responding to sucrose and corn oil in the brief access lick paradigm, a test measuring a combination of mainly taste-guided "liking" and low-effort "wanting", as well as 4 h intake of sucrose solution. These effects were not due to nonspecific permanent neuronal changes, as they were fully reversible. We conclude that endogenous mu-opioid signaling in the nucleus accumbens is necessary for the full display of palatable food-induced hyperphagia through mechanisms including hedonic, motivational, and reinforcement processes. Development of obesity could be the result of predisposing innate differences in these mechanisms or overstimulation of these mechanisms by external factors.
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“We have recently demonstrated that nucleus accumbens injection of a μ-opioid receptor antagonist transiently suppressed such sucrose-evoked positive hedonic orofacial reactions ([158](#B158)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [158]
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Castro, D. C., & Berridge, K. C. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4458-13.2014 · Cited by 395
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275
Self-citationHormonal and neural mechanisms of food reward, eating behaviour and obesity
Murray, S. M., Tulloch, A. J., Gold, M. S., & Avena, N. M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.91 · Cited by 275
Naltrexone/bupropion for obesity: An investigational combination pharmacotherapy for weight loss
Billes, S. K., Sinnayah, P., & Cowley, M. A. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.04.004 · Cited by 255
Peciña, S., & Berridge, K. C. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12174 · Cited by 216
Metadata
- Authors
- Shin, A. C., Pistell, P. J., Phifer, C. B., & Berthoud, H. R.
- Affiliations
- Pennington Biomedical Research Center (US)
- Northwestern State University (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 170
- Issue
- 2
- Pages
- 580-588
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2933316
- OpenAlex
- W2104979095
- Cited by
- 109
- References
- 65
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 1 · 2021: 2 · 2020: 47 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 9 · 2012: 6
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK071082, DK047348)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- mu-opioid receptor, nucleus accumbens shell, food reward, incentive motivation, beta-funaltrexamine, hyperphagia, obesity
- MeSH terms
- Animals, Appetitive Behavior, Male, Microinjections, Motivation, Naltrexone, Nucleus Accumbens, Reinforcement, Psychology, Reward, Sucrose, Rats, Sprague-Dawley, Receptors, Opioid, mu, Rats
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