Dopamine D3 receptor deletion or blockade attenuates cocaine-induced conditioned place preference in mice

NEUROPHARMACOLOGY

卷:72

Article

Song, Rui^1,2  Zhang, Hai-Ying¹  Peng, Xiao-Qing¹  Su, Rui-Bin²  Yang, Ri-Fang²  Li, Jin²  Xi, Zheng-Xiong¹  Gardner, Eliot L.¹ 

[1] NIDA, Intramural Res Program, Baltimore, MD 21224 USA

[2] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

关键词: Cocaine;    Dopamine;    D-3 receptor;    YQA-14;    Reward;    Conditioned place preference;   

DOI  :  10.1016/j.neuropharm.2013.04.042

来源: Elsevier

【 摘 要 】

The dopamine (DA) D-3 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 D-3 receptor-knockout (D-3(-/-)) 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 D-3(-/-) mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D(3)Rs by YQA-14, a novel DA D-3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D-3(-/-) mice. These findings suggest that: 1) D(3)Rs 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. Published by Elsevier Ltd.

【 授权许可】

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