Increased vulnerability to cocaine in mice lacking dopamine D3 receptors

Rui Song, Hai Ying Zhang, Xia Li, Guo Hua Bi, Eliot L. Gardner, Zheng Xiong Xi

Research output: Contribution to journalArticle


Neuroimaging studies using positron emission tomography suggest that reduced dopamine D2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D3 receptors (D3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D3R KO (D3-/-) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D3-/- mice. In addition, D3-/- mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D3R deletion increases vulnerability to cocaine, and that reduced D3R availability in the brainmay constitute a risk factor for the development of cocaine addiction.

Original languageEnglish (US)
Pages (from-to)17675-17680
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - Oct 23 2012


  • Etiology of addiction
  • Extinction
  • Reinforcement
  • Reinstatement
  • Susceptibility to cocaine

ASJC Scopus subject areas

  • General

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