Lin A M, Chai C Y
Institute of Biomedical Sciences, Academia Sinica, Nangkang, Taipei, Taiwan, R.O.C.
Brain Res. 1995 Oct 23;696(1-2):15-20. doi: 10.1016/0006-8993(95)00688-m.
This study was undertaken to dynamically examine the effects of ethanol on the striatal dopaminergic transmission, in terms of N-methyl-D-aspartate (NMDA)-evoked dopamine release and dopamine uptake. In the striatum of urethane-anesthetized Sprague-Dawley rats, extracellular dopamine was measured using in vivo electrochemical detection coupled with a nafion-coated carbon fiber working electrode. Micro-ejection of NMDA evoked a transient dopamine release from the dopamine-containing nerve terminals in striatum. Local application of ethanol by pressure ejection did not elicit significant changes in spontaneous dopamine release. However, with ethanol pretreatment, the time course of NMDA-induced dopamine release was markedly prolonged while the magnitude and the rate of clearance were significantly reduced. These effects were compared to those of nomifensine, a dopamine uptake blocker. Nominfensine pretreatment was found to augment the time course of NMDA-evoked dopamine release analogous to those by ethanol pretreatment. Furthermore, pretreatment with ethanol did not increase the time course parameters of dopamine signals if dopamine releases were induced by co-application of NMDA and nominfensine. These data suggest that in addition to the attenuation of NMDA-evoked dopamine release, ethanol inhibits dopamine uptake in a similar fashion to that observed with nomifensine in situ in the striatum. Indeed, ethanol altered the uptake of exogenous dopamine from the extracellular space of striatal cortex. The time course of dopamine signals was prolonged and the rate of clearance was reduced after ethanol treatment. Taken together, our data demonstrate that ethanol simultaneously inhibits NMDA-evoked dopamine release and dopamine uptake in the striatum, suggesting the importance of the interplay between release and uptake in ethanol effects on striatal dopaminergic transmission.
本研究旨在从N-甲基-D-天冬氨酸（NMDA）诱发的多巴胺释放和多巴胺摄取方面，动态检测乙醇对纹状体多巴胺能传递的影响。在乌拉坦麻醉的Sprague-Dawley大鼠的纹状体中，使用体内电化学检测结合涂有nafion的碳纤维工作电极测量细胞外多巴胺。微量注射NMDA可诱发纹状体中含多巴胺神经末梢的短暂多巴胺释放。通过压力喷射局部应用乙醇不会引起自发多巴胺释放的显著变化。然而，乙醇预处理后，NMDA诱导的多巴胺释放的时间进程显著延长，而释放量和清除率显著降低。将这些效应与多巴胺摄取阻滞剂诺米芬辛的效应进行了比较。发现诺米芬辛预处理可增强NMDA诱发的多巴胺释放的时间进程，类似于乙醇预处理的效果。此外，如果多巴胺释放是由NMDA和诺米芬辛共同应用诱导的，乙醇预处理不会增加多巴胺信号的时间进程参数。这些数据表明，除了减弱NMDA诱发的多巴胺释放外，乙醇还以与纹状体原位观察到的诺米芬辛类似的方式抑制多巴胺摄取。事实上，乙醇改变了纹状体皮质细胞外空间中外源性多巴胺的摄取。乙醇处理后，多巴胺信号的时间进程延长，清除率降低。综上所述，我们的数据表明乙醇同时抑制纹状体中NMDA诱发的多巴胺释放和多巴胺摄取，提示释放和摄取之间的相互作用在乙醇对纹状体多巴胺能传递影响中的重要性。
