Morari M, O'Connor W T, Ungerstedt U, Fuxe K
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Eur J Pharmacol. 1994 Apr 11;256(1):23-30. doi: 10.1016/0014-2999(94)90611-4.
The effects of local perfusion with the dopamine D1 receptor antagonist SCH 23390 and the dopamine D2 receptor antagonist raclopride on basal and N-methyl-D-aspartate (NMDA) stimulated dopamine, gamma-aminobutyric acid (GABA) and glutamate levels in the dorsolateral striatum were monitored using in vivo microdialysis in the halothane anaesthetized rat. Local perfusion (90 min) with SCH 23390 and raclopride (1 and 10 microM) dose dependently increased basal striatal dopamine release whereas GABA and glutamate dialysate levels were unaffected. Local perfusion (10 min) with the 1 mM concentration of NMDA increased striatal dopamine, GABA and glutamate outflow. However, when perfused together with SCH 23390 (1 microM) NMDA inhibited glutamate efflux. Moreover, in the presence of SCH 23390 (10 microM) the NMDA induced rise in dopamine and GABA levels was partly prevented. On the other hand, raclopride 1 microM enhanced the NMDA stimulated GABA efflux while at 10 microM it partly counteracted the NMDA induced dopamine release. These data demonstrate that NMDA induced changes in striatal neurotransmitter outflow are effectively modified by dopamine D1 and D2 receptor blockade.
在氟烷麻醉的大鼠中，采用体内微透析技术监测多巴胺D1受体拮抗剂SCH 23390和多巴胺D2受体拮抗剂雷氯必利对背外侧纹状体基础状态以及N-甲基-D-天冬氨酸（NMDA）刺激下多巴胺、γ-氨基丁酸（GABA）和谷氨酸水平的影响。用SCH 23390和雷氯必利（1和10微摩尔）进行局部灌注（90分钟），剂量依赖性地增加了纹状体基础多巴胺释放，而GABA和谷氨酸透析液水平未受影响。用1毫摩尔浓度的NMDA进行局部灌注（10分钟）增加了纹状体多巴胺、GABA和谷氨酸的流出。然而，当与SCH 23390（1微摩尔）一起灌注时，NMDA抑制了谷氨酸外流。此外，在存在SCH 23390（10微摩尔）的情况下，NMDA诱导的多巴胺和GABA水平升高被部分阻止。另一方面，1微摩尔的雷氯必利增强了NMDA刺激的GABA外流，而在10微摩尔时，它部分抵消了NMDA诱导的多巴胺释放。这些数据表明，NMDA诱导的纹状体神经递质流出变化可被多巴胺D1和D2受体阻断有效改变。
