Lin A M, Chai C Y
Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, ROC.
Neurosci Res. 1998 Jul;31(3):171-7. doi: 10.1016/s0168-0102(98)00036-4.
An involvement of dopamine uptake in the N-methyl-D-aspartate (NMDA)-modulated dopaminergic transmission in rat striatum was studied using the technique of in vivo electrochemical detection. Microinjection of potassium (K+) evoked dopamine overflows from the dopamine-containing nerve terminals in the striatum. While application of NMDA did not evoke any dopamine overflow, co-application of NMDA and K+ induced larger dopamine overflows than those by K+ alone. Furthermore, dynamic analysis showed that the rate of clearance (Tc) was reduced by NMDA. Indeed, our uptake study demonstrated an NMDA-induced inhibition of dopamine clearance. The time course of electrochemical signals evoked by microinjection of exogenous dopamine was increased and Tc was reduced following NMDA application. In order to delineate the effects of NMDA on K(+)-evoked dopamine overflows and/or on dopamine uptake, nomifensine, a dopamine uptake inhibitor was used. Application of nomifensine potentiated K(+)-evoked dopamine overflows. Co-administration of NMDA further augmented dopamine overflows by the K+ and nomifensine mixture. Taken together, our data suggest that NMDA concomitantly potentiated dopamine overflows in response to depolarizing stimuli and attenuated dopamine uptake. The increment by NMDA of K(+)-evoked dopamine overflows may partially result from an attenuated dopamine uptake in rat striatum.
利用体内电化学检测技术，研究了多巴胺摄取在大鼠纹状体中N-甲基-D-天冬氨酸（NMDA）调节的多巴胺能传递中的作用。微量注射钾离子（K+）可引起纹状体中含多巴胺神经末梢的多巴胺释放。虽然应用NMDA不会引起任何多巴胺释放，但NMDA和K+共同应用所诱导的多巴胺释放量比单独使用K+时更大。此外，动态分析表明，NMDA可降低清除率（Tc）。实际上，我们的摄取研究表明，NMDA可诱导多巴胺清除受到抑制。在应用NMDA后，微量注射外源性多巴胺所诱发的电化学信号的时间进程延长，且Tc降低。为了阐明NMDA对K+诱发的多巴胺释放和/或多巴胺摄取的影响，使用了多巴胺摄取抑制剂诺米芬辛。应用诺米芬辛可增强K+诱发的多巴胺释放。NMDA与K+和诺米芬辛混合物共同给药可进一步增强多巴胺释放。综上所述，我们的数据表明，NMDA可同时增强对去极化刺激的多巴胺释放，并减弱多巴胺摄取。NMDA使K+诱发的多巴胺释放增加，这可能部分是由于大鼠纹状体中多巴胺摄取减弱所致。
