Finkelstein J E, Hengemihle J M, Ingram D K, Petri H L
Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Johns Hopkins Medical Institutions, Baltimore, MD 21224.
Pharmacol Biochem Behav. 1994 Nov;49(3):707-10. doi: 10.1016/0091-3057(94)90091-4.
The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor appears to be involved with processes of learning and memory. A neutral amino acid binding site is known to exist on the NMDA complex. Glycine binds with high affinity to this site and has been found to potentiate NMDA activity. 2-N-Pentylaminoacetamide HCl (milacemide) is a glycine agonist that has been found to enhance performance of rodents in passive and active avoidance tasks and has improved the performance of humans in several word retrieval tasks. We evaluated the effects of milacemide on the performance of male C57BL/6J mice in a complex spatial task, the Morris water maze. Because NMDA receptor activation appears involved in induction of long-term potentiation, it was hypothesized that milacemide administration would be involved in task acquisition. Therefore, mice were treated with either milacemide (10 mg/kg) or vehicle 1 h prior to training on each of 4 consecutive days. Results indicated that mice treated with milacemide learned the task significantly faster than controls over 4 days of training, as measured by mean distance (cm) to reach the goal platform. Therefore, agonism of the glycine site on the NMDA receptor appears to facilitate performance of learning in a spatial memory task.
谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型似乎与学习和记忆过程有关。已知在NMDA复合物上存在一个中性氨基酸结合位点。甘氨酸以高亲和力与该位点结合，并已被发现可增强NMDA活性。2-N-戊基氨基乙酰胺盐酸盐（米拉酰胺）是一种甘氨酸激动剂，已被发现可提高啮齿动物在被动和主动回避任务中的表现，并改善人类在多项单词检索任务中的表现。我们评估了米拉酰胺对雄性C57BL/6J小鼠在复杂空间任务——莫里斯水迷宫中的表现的影响。由于NMDA受体激活似乎参与了长时程增强的诱导，因此推测米拉酰胺给药会参与任务习得。因此，在连续4天的训练中，每天训练前1小时，给小鼠注射米拉酰胺（10 mg/kg）或赋形剂。结果表明，在4天的训练中，用米拉酰胺治疗的小鼠比对照组学习任务的速度明显更快，以到达目标平台的平均距离（厘米）衡量。因此，NMDA受体上甘氨酸位点的激动作用似乎有助于在空间记忆任务中的学习表现。
