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Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats

Nature Neuroscience volume 13, pages 635641 (2010) | Download Citation

  • A Corrigendum to this article was published on 01 August 2010

This article has been updated

Abstract

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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Change history

  • 09 July 2010

    In the version of this article initially published, two citations were inadvertently omitted. To correct this, the following sentence was inserted after the sixth sentence in the introduction (first paragraph, line 16): "In rats, both susceptibility to obesity and diet-induced obesity have been linked to deficits in mesolimbic dopamine signaling, with obesity-susceptible animals exhibiting reduced levels of D2 receptors50,51."  These references have been added to the reference list as follows:  50. Geiger, B.M. et al. Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats. FASEB J22, 2740–2746 (2008).  51. Geiger, B.M. et al. Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience 10, 1193–1199 (2009).  The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This work was supported by a Bank of America Fellowship (P.M.J.), the Landenberger Foundation (P.J.K.) and a grant from the US National Institutes of Health (DA025983; P.J.K.). This is publication number 19,563 from the Scripps Research Institute.

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Affiliations

  1. Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute-Scripps Florida, Jupiter, Florida, USA.

    • Paul M Johnson
    •  & Paul J Kenny

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Contributions

P.M.J. conducted all experiments. P.M.J. and P.J.K. designed the experiments, analyzed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Paul J Kenny.

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DOI

https://doi.org/10.1038/nn.2519

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