Dopamine D(3) receptor deletion or blockade attenuates cocaine-induced conditioned place preference in mice.
Dopamine D(3) receptor deletion or blockade attenuates cocaine-induced conditioned place preference in mice.
复制标题
DOI：
10.1016/j.neuropharm.2013.04.042
复制
发表时间：
2013-09
影响因子：
4.7
通讯作者：
Gardner EL
中科院分区：
文献类型：
--
作者：
Song R;Zhang HY;Peng XQ;Su RB;Yang RF;Li J;Xi ZX;Gardner EL
多巴胺（DA）D3受体（D3 R）在治疗成瘾的药物开发中受到广泛关注。然而，D3 R在药物奖赏和成瘾中的功能作用一直是一个有争议的问题。我们最近报道，D3受体敲除（D3−/−）小鼠对可卡因自我给药的脆弱性增加，我们将其解释为D3 R缺失后对可卡因奖励减弱的补偿反应。在这里，我们报告说，与野生型小鼠相比，D3−/−小鼠表现出减弱的可卡因诱导的条件性位置反应（CPP）。类似地，一种新型DA D3受体拮抗剂YQA-14阻断脑D3受体，可显著且剂量依赖性地抑制可卡因诱导的CPP在WT小鼠中的获得和表达，但在D3−/−小鼠中则不然。这些研究结果表明：1）D3 R在介导可卡因奖赏效应中起重要作用; 2）YQA-14是一种高效、选择性的D3 R拮抗剂，作为治疗可卡因成瘾的候选药物值得进一步研究。
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 cocaine-induced 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.
登录
查看更多内容
影响因子：
3.4
作者：
Le Foll, B;Francès, H;Sokoloff, P
通讯作者：
Sokoloff, P
影响因子：
5.3
作者：
Caine, S. Barak;Thomsen, Morgane;Xu, Ming
通讯作者：
Xu, Ming
影响因子：
3.4
作者：
Lamas, X;Negus, SS;Mello, NK
通讯作者：
Mello, NK
影响因子：
3.4
作者：
Song R;Yang RF;Wu N;Su RB;Li J;Peng XQ;Li X;Gaál J;Xi ZX;Gardner EL
通讯作者：
Gardner EL
影响因子：
3.3
作者：
DIAZ, J;LEVESQUE, D;SOKOLOFF, P
通讯作者：
SOKOLOFF, P