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CRF system recruitment mediates dark side of compulsive eating
Open accessAbstract
Dieting to control body weight involves cycles of deprivation from palatable food that can promote compulsive eating. The present study shows that rats withdrawn from intermittent access to palatable food exhibit overeating of palatable food upon renewed access and an affective withdrawal-like state characterized by corticotropin-releasing factor-1 (CRF 1 ) receptor antagonist-reversible behaviors, including hypophagia, motivational deficits to obtain less palatable food, and anxiogenic-like behavior. Withdrawal was accompanied by increased CRF expression and CRF 1 electrophysiological responsiveness in the central nucleus of the amygdala. We propose that recruitment of anti-reward extrahypothalamic CRF-CRF 1 systems during withdrawal from palatable food, analogous to abstinence from abused drugs, may promote compulsive selection of palatable food, undereating of healthier alternatives, and a negative emotional state when intake of palatable food is prevented.
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In the citing paper
“A background of ELA may potentiate food addiction behaviours in some individuals, especially within the context of an environment rich in highly processed, calorie dense and extremely palatable food 4, 21, 22.”
From History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity (2019) · cites this paper as [22]
In the citing paper
“Overindulgence of foods rich in fat and sugar has been shown to reduce CNS reward thresholds, resulting in a drive for higher intake of such palatable foods to achieve similar levels of satisfaction 22.”
From History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity (2019) · cites this paper as [22]
In the citing paper
“exposure to high fats diets, yo–yo dieting and withdrawal from such diets, may alter extrahypothalamic CRF pathways involved in the regulation of stress responses and also disrupt brain reward motivation responses to increase compulsive food seeking and stress-induced HP food seeking”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Cottone et al., 2009
In the citing paper
“Overconsumption of HP food intake is also known to reduce reward thresholds along with an upregulation of the extrahypothalamic Corticotrophin Releasing Factor (CRF) in the amygdala and related limbic striatal pathways, which, in turn, may promote food craving and associated greater neural reactivity to food cues in these brain regions thereby increasing risk of overeating of HP foods”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Cottone et al., 2009
In the citing paper
“Increased drug taking and high fat diets alter CRF, GC and noradrenergic activity to increase sensitization of reward pathways (including the ventral tegmental area [VTA], nucleus accumbens [NAc], dorsal striatum and the mPFC regions) which influences preference for addictive substances and HP foods and increases drug/food craving and intake”
From Role of addiction and stress neurobiology on food intake and obesity (2018) · cites this paper as Cottone et al., 2009
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Metadata
- Authors
- Cottone, P., Sabino, V., Roberto, M., Bajo, M., Pockros, L., Frihauf, J. B., Fekete, E. M., Steardo, L., Rice, K. C., Grigoriadis, D. E., Conti, B., Koob, G. F., & Zorrilla, E. P.
- Affiliations
- Boston University (US)
- Neurological Research Institute (US)
- Scripps Research Institute (US)
- Committee on the Neurobiology of Addictive Disorders,
- University of California San Diego (US)
- Sapienza University of Rome (IT)
- National Institute on Drug Abuse (US)
- Neurocrine Biosciences (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-11-24
- Volume
- 106
- Issue
- 47
- Pages
- 20016-20020
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2785284
- OpenAlex
- W2005352154
- Cited by
- 192
- References
- 27
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 16 · 2020: 15 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 10 · 2015: 10 · 2014: 14 · 2013: 21 · 2012: 18
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA016985, AA 015566, AA016731, K99AA016731, R01AA015566, R00AA016731)
- National Institute on Aging (AG028040, R01AG028040)
- National Heart, Lung, and Blood Institute (HL088083, R21HL088083)
- National Institute on Drug Abuse (R00DA023680, R01DA030425, DA023680, K99DA023680)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, R01DK070118, P01DK026741, DK70118, P30-DK56336, P30DK056336)
- National Institute of Neurological Disorders and Stroke (IT32NS061847-01A2, T32NS061847)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- compulsive eating, corticotropin-releasing factor, CRF1 receptor, food withdrawal, palatable food, dieting, anxiogenic-like behavior, central amygdala, hypophagia, motivational deficits
- MeSH terms
- CRF Receptor, Type 1, Amygdala, Animals, Behavior, Animal, Compulsive Behavior, Corticotropin-Releasing Hormone, Diet, Eating, Electrophysiology, Male, Pyrimidines, Reward, Stress, Psychological, Substance Withdrawal Syndrome, Behavior, Addictive, Rats, Wistar, Receptors, Corticotropin-Releasing Hormone, Maze Learning, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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