Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Biol Pharm Bull. 2010;33(3):439-43. doi: 10.1248/bpb.33.439.
To clarify the interaction between hippocampal gamma-aminobutyric acid (GABA)(A) receptor and N-methyl-D-aspartate (NMDA) receptor in the retention of spatial working memory, the effects of muscimol, (+)MK-801, cyclosporin A and combined use of these drugs were studied on the retention of spatial working memory in a delayed spatial win-shift (SWSh) task. Intrahippocampal injection of muscimol at a dose of 3 nmol/side caused a significant decrease in the number of correct choices and an increase in the number of across-phase errors. On the other hand, (+)MK-801 showed no significant effect on the number of correct choices, across-phase errors and within-phase errors, even at a dose of 1.5 nmol/side; however, (+)MK-801 1.5 nmol/side significantly potentiated the effect of muscimol observed at a dose of 3 nmol/side on the number of correct choices and across-phase errors. Cyclosporin A at a dose of 3 nmol/side, which showed no effect when used separately, significantly potentiated the effect of muscimol observed at a dose of 3 nmol/side. These results indicate that hippocampal NMDA receptors regulate the effect of spatial working memory induced by muscimol. In addition, calcineurin may be involved in muscimol-induced impairment of memory retention.
为了阐明海马γ-氨基丁酸（GABA）（A）受体与 N-甲基-D-天冬氨酸（NMDA）受体在空间工作记忆保留中的相互作用，研究了 muscimol、（+）MK-801、环孢菌素 A 以及这些药物联合使用对延迟空间工作记忆的影响 - 移位（SWSh）任务中的空间工作记忆保留。海马内注射 3 nmol/侧的 muscimol 可显著减少正确选择的数量并增加跨相位错误的数量。另一方面，（+）MK-801 即使在 1.5 nmol/侧的剂量下，对正确选择的数量、跨相位错误和同相位错误也没有显著影响；然而，（+）MK-801 1.5 nmol/侧显著增强了 3 nmol/侧 muscimol 观察到的对正确选择的数量和跨相位错误的影响。单独使用时无作用的 3 nmol/侧环孢菌素 A 显著增强了 3 nmol/侧 muscimol 观察到的作用。这些结果表明，海马 NMDA 受体调节 muscimol 诱导的空间工作记忆效应。此外，钙调神经磷酸酶可能参与了 muscimol 诱导的记忆保留损伤。
