Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity
Open accessAbstract
Increased caloric intake in dietary obesity could be driven by central mechanisms that regulate reward-seeking behavior. The mesolimbic dopamine system, and the nucleus accumbens in particular, underlies both food and drug reward. We investigated whether rat dietary obesity is linked to changes in dopaminergic neurotransmission in that region. Sprague-Dawley rats were placed on a cafeteria-style diet to induce obesity or a laboratory chow diet to maintain normal weight gain. Extracellular dopamine levels were measured by in vivo microdialysis. Electrically evoked dopamine release was measured ex vivo in coronal slices of the nucleus accumbens and the dorsal striatum using real-time carbon fiber amperometry. Over 15 weeks, cafeteria-diet fed rats became obese (>20% increase in body weight) and exhibited lower extracellular accumbens dopamine levels than normal weight rats (0.007+/-0.001 vs. 0.023+/-0.002 pmol/sample; P<0.05). Dopamine release in the nucleus accumbens of obese rats was stimulated by a cafeteria-diet challenge, but it remained unresponsive to a laboratory chow meal. Administration of d-amphetamine (1.5 mg/kg i.p.) also revealed an attenuated dopamine response in obese rats. Experiments measuring electrically evoked dopamine signal ex vivo in nucleus accumbens slices showed a much weaker response in obese animals (12 vs. 25x10(6) dopamine molecules per stimulation, P<0.05). The results demonstrate that deficits in mesolimbic dopamine neurotransmission are linked to dietary obesity. Depressed dopamine release may lead obese animals to compensate by eating palatable "comfort" food, a stimulus that released dopamine when laboratory chow failed.
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Preclinical and clinical studies provide evidence of decreases in striatal D2R that are linked with reward through the NAc and with habits and routines through the dorsal striatum in obesity.
“Both preclinical and clinical studies have provided evidence of decreases in striatal D2R, which, through the NAc, are linked with reward and through the dorsal striatum with the establishment of habits and routines in obesity (80–82).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [80]
Dysregulation of striatal D2R signaling has been implicated in obesity and compulsive food intake in obese rodents.
“Dysregulation of striatal D2R signaling has also been implicated in obesity (76,77) and in compulsive food intake in obese rodents (78).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [77]
Both preclinical and clinical studies have provided evidence of decreased striatal D2R signaling in obesity, which is linked with reward in the NAc but also with the establishment of habits and routines in the dorsal striatum.
“Both preclinical and clinical studies have provided evidence of decreased striatal D2R signaling, which, as mentioned above, is linked with reward (NAc) but also with the establishment of habits and routines (dorsal striatum) in obesity (Geiger et al 2009;Wang et al 2001).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Geiger et al 2009
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- Authors
- Geiger, B. M., Haburcak, M., Avena, N. M., Moyer, M. C., Hoebel, B. G., & Pothos, E. N.
- Affiliations
- Tufts University (US)
- Princeton University (US)
- Corresponding author
- Pothos, E.N.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 159
- Issue
- 4
- Pages
- 1193-1199
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2677693
- OpenAlex
- W1985107350
- Cited by
- 403
- References
- 29
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 7 · 2023: 14 · 2022: 19 · 2021: 32 · 2020: 17 · 2019: 24 · 2018: 19 · 2017: 37 · 2016: 33 · 2015: 39 · 2014: 28 · 2013: 17 · 2012: 34
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Center for Neuroscience Research
- Richard and Susan Smith Family Foundation (P30 NS047243)
- 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
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- diet-induced obesity, mesolimbic dopamine system, nucleus accumbens, dopamine release, cafeteria diet, food reward, reward-seeking behavior, amphetamine response, dorsal striatum, energy intake, comfort food
- MeSH terms
- Animals, Central Nervous System Agents, Corpus Striatum, Dextroamphetamine, Diet, Dopamine, Extracellular Space, Feeding Behavior, Female, Limbic System, Synaptic Transmission, Nucleus Accumbens, Obesity, Potassium Chloride, Rats, Sprague-Dawley, Dopamine Uptake Inhibitors, Rats, In Vitro Techniques
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