谷氨酸脱羧酶抑制剂L－苹果酸对小鼠学习记忆的影响

EFFECTS OF L-MALATE,AN INHIBITOR OF GLUTAMATE DECARBOXYLASE,ONL LEARNING AND MEMORY IN MICE

跳台法和Ｙ迷宫法试验表明，小鼠ｐｏＬ－苹果酸６００ｍｇ·ｋｇ－１连续５ｄ后对记忆的获得、巩固和再现均有明显的改善作用，并能促进空间辨别学习能力；Ｌ－苹果酸改善记忆的作用能被ＮＭＤＡ受体桔抗剂氯胺酮所桔抗。脑内游离氨基酸测定显示，Ｌ－苹果酸可明显降低小鼠脑内ＧＡＢＡ水平，提高Ｇｌｕ／ＧＡＢＡ比值。实验结果表明，脑内ＧＡＢＡ水平下降，Ｇｌｕ／ＧａｎＡ比值升高对学习记忆有正性调节作用。

Oral administration of L-malate 600 mg· kg-1 for 5 days before training cansignificantly promote memory acquisition,consolidation and retrieval,respectively,on anisodine-,chloramphenicoL-,and ethanOl-induced memory impaiiment in mice,Ketamine(8.5mg· kg-1,ip),aselective NMDA receptor antagonist,was found to inhibit the anti-amnesic activity of L-malate. Theglutamate(Glu)and GABA content in mice brain was measured by high-perfonnance liquidchromatography with fluorescence detection. The content of GABA was shown to be decreased frOm2.3±0.5umol·g-1 to l.3 ±0.5 umol·g-1 (P<0.01),sO the Glu/GABA ratio was increasedsignificantly. These resuIts suggest that the decrease of cerebral GABA Ievel and the increase of Glu/GABA ratio is favorable to learning and memory.