Cooperative Activation of Dopamine D1 and D2 Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein βγ Subunits
Cooperative Activation of Dopamine D1 and D2 Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein βγ Subunits
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DOI：
10.1523/jneurosci.23-12-05079.2003
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发表时间：
2003-06
期刊：
影响因子：
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通讯作者：
F. Hopf;M. Cascini;Adrienne S. Gordon;I. Diamond;A. Bonci
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文献类型：
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作者：
F. Hopf;M. Cascini;Adrienne S. Gordon;I. Diamond;A. Bonci
伏隔核中的多巴胺调节动机和成瘾行为。多巴胺D1和D2受体通常被认为在细胞水平上发挥相反的作用，但许多行为学研究发现，D1和D2受体在丘脑核中具有明显的协同作用。在这里，我们表明，多巴胺诱导的脑片中的丘脑核神经元的尖峰放电的增强需要D1和D2受体。D1和D2受体协同作用的一种细胞内机制可能是由Gi/o连接的D2受体释放的G蛋白βγ亚基（Gβγ）与D1受体的Gα s样亚基结合激活腺苷酸环化酶的特定亚型。在这方面，蛋白激酶A或Gβγ抑制剂可阻止多巴胺能增强锋电位放电。此外，细胞内灌流Gβγ可激活D1受体，但不能激活D2受体，从而增强锋电位放电。最后，我们的数据表明，这些途径可能会通过抑制缓慢的A型钾电流来增加尖峰放电。这些结果提供了证据的一种新的细胞机制，通过D1和D2受体的协同作用，在延髓核可以介导多巴胺依赖性行为。
Dopamine in the nucleus accumbens modulates both motivational and addictive behaviors. Dopamine D1 and D2 receptors are generally considered to exert opposite effects at the cellular level, but many behavioral studies find an apparent cooperative effect of D1 and D2 receptors in the nucleus accumbens. Here, we show that a dopamine-induced enhancement of spike firing in nucleus accumbens neurons in brain slices required both D1 and D2 receptors. One intracellular mechanism that might underlie cooperativity of D1 and D2 receptors is activation of specific subtypes of adenylyl cyclases by G-protein βγ subunits (Gβγ) released from the Gi/o-linked D2 receptor in combination with Gαs-like subunits from the D1 receptor. In this regard, dopaminergic enhancement of spike firing was prevented by inhibitors of protein kinase A or Gβγ. Furthermore, intracellular perfusion with Gβγ enabled D1 receptor activation but not D2 receptor activation to enhance spike firing. Finally, our data suggest that these pathways may increase spike firing by inhibition of a slow A-type potassium current. These results provide evidence for a novel cellular mechanism through which cooperative action of D1 and D2 receptors in the nucleus accumbens could mediate dopamine-dependent behaviors.