Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats
Open accessAbstract
We found that development of obesity was coupled with emergence of a progressively worsening deficit in neural reward responses. Similar changes in reward homeostasis induced by cocaine or heroin are considered to be crucial in triggering the transition from casual to compulsive drug-taking. Accordingly, we detected compulsive-like feeding behavior in obese but not lean rats, measured as palatable food consumption that was resistant to disruption by an aversive conditioned stimulus. Striatal dopamine D2 receptors (D2Rs) were downregulated in obese rats, as has been reported in humans addicted to drugs. Moreover, lentivirus-mediated knockdown of striatal D2Rs rapidly accelerated the development of addiction-like reward deficits and the onset of compulsive-like food seeking in rats with extended access to palatable high-fat food. These data demonstrate that overconsumption of palatable food triggers addiction-like neuroadaptive responses in brain reward circuits and drives the development of compulsive eating. Common hedonic mechanisms may therefore underlie obesity and drug addiction.
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Decreased striatal D2R availability has been linked to compulsive food intake in obese rodents and with decreased metabolic activity in OFC and ACC in obese humans.
“decreased striatal D2R availability has been linked to compulsive food intake in obese rodents (84) and with decreased metabolic activity in OFC and ACC in obese humans (63).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [84]
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 [78]
Drugs and alcohol increase feelings of reward in the short term but decrease it in the long term.
“Drugs and alcohol increase feelings of reward in the short term but decrease it in the long term.175–179”
From Early life adversity and health-risk behaviors: Proposed psychological and neural mechanisms (2018) · cites this paper as [179]
In rodents, regular intake of high-fat and high-sugar foods leads to downregulation of postsynaptic D2 receptors.
“In rodents, regular intake of high-fat and high-sugar foods leads to downregulation of postsynaptic D2 receptors.177–179”
From Early life adversity and health-risk behaviors: Proposed psychological and neural mechanisms (2018) · cites this paper as [179]
Decreased striatal D2R availability has been linked to compulsive food intake in obese rodents and with decreased metabolic activity in OFC and ACC in obese humans.
“Importantly, decreased striatal D2R availability has been linked to compulsive food intake in obese rodents (Johnson and Kenny 2010) and with decreased metabolic activity in OFC and ACC in obese humans (Volkow et al 2008b) (Fig. 7 a-c).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Johnson and Kenny 2010
In Wistar rats, exposure to a palatable cafeteria diet led to sustained hyperphagia over 40 days and lateral hypothalamic electrical self-stimulation threshold increased in parallel to body weight gain.
“In Wistar rats, exposure to a palatable cafeteria diet led to sustained hyperphagia over 40 days and lateral hypothalamic electrical self-stimulation threshold increased in parallel to body weight gain ([89](#B89)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [89]
Dopamine D2-receptor expression in the dorsal striatum was significantly reduced in parallel to worsening of the reward threshold, to levels found in cocaine-addicted rats.
“Furthermore, dopamine D2-receptor expression in the dorsal striatum was significantly reduced in parallel to worsening of the reward threshold ([89](#B89)), to levels found in cocaine-addicted rats ([35](#B35)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [89]
After 14 days of abstinence from the palatable diet, reward threshold did not normalize even though the rats were hypophagic and lost ∼10% body weight.
“Interestingly, after 14 days of abstinence from the palatable diet, reward threshold did not normalize even though the rats were hypophagic and lost ∼10% body weight ([89](#B89)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [89]
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- Authors
- Johnson, P. M., & Kenny, P. J.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Kenny, Paul J
- Venue
- Nature Neuroscience
- Published
- 2010-03-28
- Volume
- 13
- Issue
- 5
- Pages
- 635-641
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2947358
- OpenAlex
- W2099440512
- Cited by
- 1,495
- References
- 51
- Citations by year
- 2026: 42 · 2025: 60 · 2024: 56 · 2023: 91 · 2022: 77 · 2021: 92 · 2020: 136 · 2019: 81 · 2018: 102 · 2017: 104 · 2016: 106 · 2015: 112 · 2014: 121 · 2013: 92 · 2012: 101
- FWCI
- 40.33
- Type
- journal article
- Language
- en
- Update notices
- erratum (2010-08-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA025983, DA025983)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- dopamine D2 receptor, compulsive eating, diet-induced obesity, striatum, heroin, addiction-like behavior, neural adaptation
- MeSH terms
- Animals, Behavior, Animal, Energy Intake, Compulsive Behavior, Conditioning, Operant, Corpus Striatum, Diet, Disease Models, Animal, Electric Stimulation, Feeding Behavior, Food Preferences, Glial Fibrillary Acidic Protein, Hypothalamus, Male, Obesity, Phosphopyruvate Hydratase, Reward, RNA, Small Nuclear, Weight Gain, Down-Regulation, Behavior, Addictive, Rats, Wistar, Receptors, Dopamine D2, Green Fluorescent Proteins, Rats
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