NEUROMODULATORY ACTIONS OF DOPAMINE IN THE NEOSTRIATUM ARE DEPENDENT UPON THE EXCITATORY AMINO-ACID RECEPTOR SUBTYPES ACTIVATED
NEUROMODULATORY ACTIONS OF DOPAMINE IN THE NEOSTRIATUM ARE DEPENDENT UPON THE EXCITATORY AMINO-ACID RECEPTOR SUBTYPES ACTIVATED
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DOI：
10.1073/pnas.90.20.9576
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发表时间：
1993-10-15
影响因子：
11.1
通讯作者：
LEVINE, MS
中科院分区：
文献类型：
--
作者：
CEPEDA, C;BUCHWALD, NA;LEVINE, MS
在哺乳动物新纹状体，多巴胺调节兴奋性氨基酸受体激活介导的神经元反应。这种调节的方向随兴奋性氨基酸受体激活的特定亚型而变化。当应用多巴胺时，谷氨酸（Glu）和非N-甲基-D-天冬氨酸（NMDA）激动剂使君子酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸的离子电渗应用引起的反应显着减弱。与此相反，NMDA诱发的反应显着增强。通过水浴应用SKF 38393（一种D1受体激动剂）模拟NMDA诱发兴奋的增强。D1受体拮抗剂SCH 23390阻断多巴胺对NMDA诱导兴奋的增强作用。D2受体激动剂Quinpirole可减弱NMDA和非NMDA受体激动剂引起的反应。这些结果表明，多巴胺在新纹状体复杂的调节作用是兴奋性氨基酸受体以及特定的多巴胺受体亚型激活的功能。这些发现具有临床意义，因为多巴胺和兴奋性氨基酸的作用与神经和情感障碍有关。
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.