Li H B, Matsumoto K, Yamamoto M, Watanabe H
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Pharmacol Biochem Behav. 1997 Sep;58(1):249-53. doi: 10.1016/s0091-3057(97)00015-4.
The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists CGS19755 and MK801 and the 2-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist YM90K on spatial working memory were investigated by using a delay-interposed radial-arm maze (RAM) task in rats. CGS19755 and MK801, at the largest dose that had no effect on the performance in the nondelayed RAM task, significantly decreased the initial correct response after the 5-min delay in the delay-interposed RAM task. In contrast, YM90K had no effect on the initial correct response and arm reentries in both the delay-interposed and nondelayed RAM task. CGS19755, MK801 and YM90K, at all doses tested, did not alter the running time in either the delayed or the nondelayed RAM tasks. These results suggest that spatial working memory can be impaired by a blockade of NMDA receptor function and that such impairment is particularly sensitive to delay interposition. The lack of effect of the AMPA receptor antagonist provides additional evidence of the importance of the NMDA subtype of the glutamate receptors in cognitive processes.
通过在大鼠中使用延迟插入式放射状臂迷宫（RAM）任务，研究了N-甲基-D-天冬氨酸（NMDA）受体拮抗剂CGS19755和MK801以及2-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体拮抗剂YM90K对空间工作记忆的影响。CGS19755和MK801在对非延迟RAM任务的表现无影响的最大剂量下，显著降低了延迟插入式RAM任务中5分钟延迟后的初始正确反应。相比之下，YM90K对延迟插入式和非延迟RAM任务中的初始正确反应和进入臂数均无影响。在所有测试剂量下，CGS19755、MK801和YM90K均未改变延迟或非延迟RAM任务中的运行时间。这些结果表明，NMDA受体功能的阻断可损害空间工作记忆，且这种损害对延迟插入尤为敏感。AMPA受体拮抗剂无作用，为谷氨酸受体的NMDA亚型在认知过程中的重要性提供了额外证据。
