Cepeda C, Buchwald N A, Levine M S
Mental Retardation Research Center, University of California, Los Angeles 90024-1759.
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9576-80. doi: 10.1073/pnas.90.20.9576.
In the mammalian neostriatum, dopamine modulates neuronal responses mediated by activation of excitatory amino acid receptors. The direction of this modulation varies with the specific subtype of excitatory amino acid receptor activated. Responses evoked by iontophoretic application of glutamate (Glu) and the non-N-methyl-D-aspartate (NMDA) agonists quisqualate and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid were significantly attenuated when dopamine was applied. In contrast, responses evoked by NMDA were markedly potentiated. The enhancement of NMDA-evoked excitations was mimicked by bath application of SKF 38393, a D1 receptor agonist. The D1 receptor antagonist SCH 23390 blocked the dopamine enhancement of NMDA-induced excitations. Quinpirole, a D2 receptor agonist, attenuated responses evoked by both NMDA and non-NMDA receptor agonists. These results indicate that the complex modulatory actions of dopamine in the neostriatum are a function of the excitatory amino acid receptor as well as the specific dopamine receptor subtype activated. These findings are of clinical relevance since the actions of dopamine and excitatory amino acids have been implicated in neurological and affective disorders.
在哺乳动物的新纹状体中，多巴胺调节由兴奋性氨基酸受体激活介导的神经元反应。这种调节的方向随所激活的兴奋性氨基酸受体的特定亚型而变化。当施加多巴胺时，通过离子电渗法施加谷氨酸（Glu）以及非N-甲基-D-天冬氨酸（NMDA）激动剂quisqualate和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸所诱发的反应会显著减弱。相比之下，NMDA所诱发的反应则明显增强。NMDA诱发兴奋的增强可通过浴加D1受体激动剂SKF 38393来模拟。D1受体拮抗剂SCH 23390可阻断多巴胺对NMDA诱导兴奋的增强作用。D2受体激动剂喹吡罗可减弱由NMDA和非NMDA受体激动剂所诱发的反应。这些结果表明，多巴胺在新纹状体中的复杂调节作用是兴奋性氨基酸受体以及所激活的特定多巴胺受体亚型的函数。这些发现具有临床相关性，因为多巴胺和兴奋性氨基酸的作用已与神经和情感障碍有关。
