Dopamine D3 receptor deletion or blockade attenuates cocaineinduced conditioned place preference in mice

Rui Song, Hai Ying Zhang, Xiao Qing Peng, Rui Bin Su, Ri Fang Yang, Jin Li, Zheng Xiong Xi, Eliot L. Gardner

Research output: Contribution to journalArticlepeer-review

Abstract

The dopamine (DA) D3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D3 receptor-knockout (D3-/-) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D3-/- mice displayed attenuated cocaineinduced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D3Rs by YQA-14, a novel DA D3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D3 -/- mice. These findings suggest that: 1) D3Rs play an important role in mediating cocaine's rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction.

Original languageEnglish (US)
Pages (from-to)82-87
Number of pages6
JournalNeuropharmacology
Volume72
DOIs
StatePublished - 2013

Keywords

  • Cocaine
  • Conditioned place preference
  • Dopamine
  • Reward
  • YQA-14

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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