A Postsynaptic Interaction between Dopamine D1 and NMDA Receptors Promotes Presynaptic Inhibition in the Rat Nucleus Accumbens via Adenosine Release-猫眼课题宝

多巴胺 D1 和 NMDA 受体之间的突触后相互作用通过腺苷释放促进大鼠伏隔核的突触前抑制

DOI：

10.1523/jneurosci.17-14-05271.1997

发表时间：

1997

期刊：

The Journal of Neuroscience

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

J. Harvey;M. G. Lacey

采用全细胞膜片钳技术，在大鼠前脑脑片上研究了多巴胺D1受体介导的对丘脑背核（NAcc）神经元的多巴胺能突触传入衰减的机制。多巴胺对单次皮层电刺激诱发的EPSC的抑制作用具有刺激依赖性。NMDA型谷氨酸受体的突触激活对于该效应是关键的，因为多巴胺诱导的EPSC抑制被竞争性NMDA受体拮抗剂1 -2-氨基-5-膦酰基戊酸（AP 5）阻断。NMDA的应用也抑制EPSC，并且这种作用和多巴胺抑制都被A1受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）阻断，暗示腺苷释放EPSC抑制。A1受体激动剂也通过突触前作用抑制EPSC，导致成对脉冲易化增加，但这对AP 5不敏感。D1受体的激活增强了由NMDA应用和孤立的NMDA受体介导的突触传递成分引起的突触后内向电流。多巴胺诱导的EPSC抑制的生化过程不涉及蛋白激酶A或cAMP及其代谢产物的产生，因为这种作用对蛋白激酶抑制剂H89和H7以及cAMP特异性磷酸二酯酶抑制剂咯利普兰具有抗性。我们的结论是，突触后D1受体的激活增强了NMDA受体的突触激活在延髓核神经元，从而促进了跨突触反馈抑制通过释放腺苷的突触能传递。对于D1受体来说，这种现象不依赖于腺苷酸环化酶的刺激而发生。这一过程可能有助于多巴胺能药物在NAcc中的运动刺激作用。

The mechanism underlying dopamine D1receptor-mediated attenuation of glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated in slices of rat forebrain, using whole-cell patch-clamp recording. The depression by dopamine of EPSCs evoked by single-shock cortical stimulation was stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was critical for this effect, because dopamine-induced EPSC depressions were blocked by the competitive NMDA receptor antagonistd/l-2-amino-5-phosphonopentanoate (AP5). Application of NMDA also depressed the EPSC, and both this effect and the dopamine depressions were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic action, causing increased paired-pulse facilitation, but this was insensitive to AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked by NMDA application and the isolated NMDA receptor-mediated component of synaptic transmission. The biochemical processes underlying the dopamine-induced EPSC depression did not involve either protein kinase A or the production of cAMP and its metabolites, because this effect was resistant to the protein kinase inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. We conclude that activation of postsynaptic D1receptors enhances the synaptic activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a transsynaptic feedback inhibition of glutamatergic synaptic transmission via release of adenosine. Unusually for D1 receptors, this phenomenon occurs independently of adenylyl cyclase stimulation. This process may contribute to the locomotor stimulant action of dopaminergic agents in the NAcc.