Martin P, Svensson A, Carlsson A, Carlsson M L
Department of Pharmacology, University of Göteborg, Sweden.
J Neural Transm Gen Sect. 1994;95(2):113-21. doi: 10.1007/BF01276430.
The present study was aimed at clarifying to what extent the hypermotility induced by the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 depends on dopamine (DA) D-1 compared to D-2 receptor tone. The D-1 receptor antagonist SCH 23390 was found to reduce locomotion to a greater extent in MK-801-treated than in vehicle-treated mice, whereas the reverse appeared to be the case for the DA D-2 receptor antagonist raclopride. In other words, MK-801-induced hyperactivity was more readily antagonized by SCH 23390 than by raclopride and, thus, DA D-1 receptors seem to be more important than D-2 receptors for MK-801-induced hyperactivity. These results are in line with our previous observation that MK-801 generally interacts synergistically with a DA D-1 but not with a D-2 receptor agonist in monoamine-depleted mice. In view of the possible role of deficient glutamatergic neurotransmission in schizophrenia, our findings underline the importance of investigating the efficacy of selective DA D-1 antagonists in this disorder.
本研究旨在阐明与D-2受体张力相比，非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801所诱导的运动亢进在多大程度上依赖于多巴胺（DA）D-1受体。研究发现，D-1受体拮抗剂SCH 23390在MK-801处理的小鼠中比在溶剂处理的小鼠中更能显著降低运动能力，而DA D-2受体拮抗剂雷氯必利的情况则相反。换句话说，与雷氯必利相比，SCH 23390更易拮抗MK-801诱导的多动，因此，对于MK-801诱导的多动，DA D-1受体似乎比D-2受体更重要。这些结果与我们之前的观察结果一致，即在单胺耗竭的小鼠中，MK-801通常与DA D-1受体激动剂协同相互作用，而不与D-2受体激动剂相互作用。鉴于谷氨酸能神经传递缺陷在精神分裂症中的可能作用，我们的研究结果强调了研究选择性DA D-1拮抗剂在该疾病中的疗效的重要性。
