Zheng P, Zhang X X, Bunney B S, Shi W X
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
Neuroscience. 1999;91(2):527-35. doi: 10.1016/s0306-4522(98)00604-6.
To examine whether dopamine modulates cortical N-methyl-D-aspartate receptor-mediated glutamate transmission, whole-cell recordings were made from identified pyramidal cells located in layers V and VI of the medial prefrontal cortex of the rat using a slice preparation. In the presence of tetrodotoxin and the absence of Mg2+, a brief local application of N-methyl-D-aspartate evoked an inward current which was blocked by the N-methyl-D-aspartate antagonist dizocilpine maleate but not affected by the non-N-methyl-D-aspartate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline, suggesting that the observed current is mediated by N-methyl-D-aspartate receptors located on recorded cells. Bath application of dopamine produced opposite effects on the N-methyl-D-aspartate current depending on the concentrations of dopamine applied. At low concentrations (<50 microM), dopamine enhanced the N-methyl-D-aspartate current, whereas at higher concentrations, dopamine suppressed the current. The same concentrations of dopamine did not significantly affect the inward current induced by the non-N-methyl-D-aspartate agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. The enhancing effect of dopamine on the N-methyl-D-aspartate response was mimicked by the D1 agonist SKF38393 and blocked by the D1 antagonist SCH31966, whereas the suppressing effect was mimicked by the D2 agonist quinpirole and blocked by the D2 antagonist eticlopride. The above results suggest that dopamine at low concentrations acts preferentially on D1-like receptors to promote N-methyl-D-aspartate receptor-mediated transmission, while at high concentrations dopamine also activates D2-like receptors, leading to a suppression of the N-methyl-D-aspartate function. This differential modulation of N-methyl-D-aspartate function may have significant implications for understanding behaviors and disorders involving both cortical dopamine- and glutamate-mediated neurotransmission.
为研究多巴胺是否调节皮质N-甲基-D-天冬氨酸受体介导的谷氨酸传递，采用脑片标本，对大鼠内侧前额叶皮质V层和VI层中已鉴定的锥体细胞进行全细胞记录。在存在河豚毒素且无Mg2+的情况下，短暂局部应用N-甲基-D-天冬氨酸可诱发内向电流，该电流可被N-甲基-D-天冬氨酸拮抗剂马来酸氯氮平阻断，但不受非N-甲基-D-天冬氨酸拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并(f)喹喔啉影响，提示观察到的电流由记录细胞上的N-甲基-D-天冬氨酸受体介导。根据所应用多巴胺的浓度，浴用多巴胺对N-甲基-D-天冬氨酸电流产生相反的作用。在低浓度（<50 microM）时，多巴胺增强N-甲基-D-天冬氨酸电流，而在较高浓度时，多巴胺抑制该电流。相同浓度的多巴胺对非N-甲基-D-天冬氨酸激动剂α-氨基-3-羟基-5-甲基异恶唑-4-丙酸诱导的内向电流无显著影响。多巴胺对N-甲基-D-天冬氨酸反应的增强作用可被D1激动剂SKF38393模拟，并被D1拮抗剂SCH31966阻断，而抑制作用可被D2激动剂喹吡罗模拟，并被D2拮抗剂依替必利阻断。上述结果表明，低浓度的多巴胺优先作用于D1样受体以促进N-甲基-D-天冬氨酸受体介导的传递，而在高浓度时多巴胺也激活D2样受体，导致N-甲基-D-天冬氨酸功能的抑制。N-甲基-D-天冬氨酸功能的这种差异调节可能对理解涉及皮质多巴胺和谷氨酸介导的神经传递的行为和疾病具有重要意义。
