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Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat
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Recent studies indicate that decreased central dopamine is associated with diet-induced obesity in humans and in animal models. In the current study, the authors assessed the hypothesis that diet-induced obesity reduces mesolimbic dopamine function. Specifically, the authors compared dopamine turnover in this region between rats fed a high-fat diet and those consuming a standard low-fat diet. The authors also assessed behavioral consequences of diet-induced obesity by testing the response of these animals in a conditioned place paradigm using amphetamine as a reinforcer and in an operant conditioning paradigm using sucrose reinforcement. Results demonstrate that animals consuming a high-fat diet, independent of the development of obesity, exhibit decreased dopamine turnover in the mesolimbic system, reduced preference for an amphetamine cue, and attenuated operant responding for sucrose. The authors also observed that diet-induced obesity with a high-fat diet attenuated mesolimbic dopamine turnover in the nucleus accumbens. These data are consistent with recent hypotheses that the hormonal signals derived from adipose tissue regulate the activity of central nervous system structures involved in reward and motivation, which may have implications for the treatment of obesity and/or addiction.
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“To this end, rodent research has revealed that prolonged high-fat diet (HFD) elicits metabolic dysfunction and increases anxiety-and depressive-like behaviors [28][29][30][31][32][33][34][35][36], heightens stress and hypothalamic-pituitary-adrenal (HPA) responses [37,38], and triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function [39][40][41].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [39]
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“findings of attenuated responses to drug rewards in animal models of obesity (33,34).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [33]
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“In selectively bred lines of obesity-prone and obesity-resistant rats, several differences in mesolimbic dopamine signaling have been reported ([41](#B41), [65](#B65)), but most of these studies used adult, already obese animals.”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [41]
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Bamba, B., Silué, S., Atayi, T. E., & Tako, A. N. (2023) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2023.115006
Desmercieres, S., Lardeux, V., Longueville, J.-E., Dugast, E., Thiriet, N., & Solinas, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.13.566808
Desmercieres, S., Lardeux, V., Longueville, J.-E., Dugast, E., Thiriet, N., & Solinas, M. (2024) · Appetite · doi:10.1016/j.appet.2024.107340
Krupa, H., Gearhardt, A. N., & Avena, N. M. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780197688908.003.0010
Metadata
- Authors
- Davis, J. F., Tracy, A. L., Schurdak, J. D., Tschöp, M. H., Lipton, J. W., Clegg, D. J., & Benoit, S. C.
- Affiliations
- University of Cincinnati (US)
- ORCID
- Venue
- Behavioral Neuroscience
- Published
- 2008-12
- Volume
- 122
- Issue
- 6
- Pages
- 1257-1263
- ISSN
- 0735-7044 (ISSN-L)
- 1939-0084
- PMC
- PMC2597276
- OpenAlex
- W2069303582
- Cited by
- 307
- References
- 50
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 10 · 2023: 12 · 2022: 11 · 2021: 24 · 2020: 19 · 2019: 10 · 2018: 20 · 2017: 13 · 2016: 26 · 2015: 37 · 2014: 21 · 2013: 24 · 2012: 21
- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioral Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK066223)
- 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 › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- high-fat diet, diet-induced obesity, amphetamine, sucrose reinforcement, conditioned place preference, nucleus accumbens, reward and motivation, adipose tissue hormones, obesity treatment, addiction
- MeSH terms
- Amphetamine, Central Nervous System Stimulants, Analysis of Variance, Animals, Behavior, Animal, Conditioning, Operant, Dietary Fats, Dopamine, Limbic System, Locomotion, Male, Reinforcement Schedule, Reward, Sucrose, Sweetening Agents, Rats, Long-Evans, Rats
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