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

Nat Neurosci. 2010 May;13(5):635-41. doi: 10.1038/nn.2519. Epub 2010 Mar 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive / etiology*
  • Behavior, Addictive / metabolism
  • Behavior, Animal
  • Compulsive Behavior / etiology*
  • Compulsive Behavior / metabolism
  • Conditioning, Operant / physiology
  • Corpus Striatum / physiology
  • Diet / adverse effects
  • Disease Models, Animal
  • Down-Regulation / physiology
  • Electric Stimulation / methods
  • Energy Intake / physiology
  • Feeding Behavior / physiology*
  • Food Preferences / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Hypothalamus / physiology
  • Male
  • Obesity / complications*
  • Obesity / etiology
  • Obesity / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Reward*
  • Weight Gain / physiology


  • Glial Fibrillary Acidic Protein
  • RNA, Small Nuclear
  • Receptors, Dopamine D2
  • Green Fluorescent Proteins
  • Phosphopyruvate Hydratase