Department of Psychology, Dickinson College, Carlisle, PA 17013, USA.
Pharmacol Biochem Behav. 2010 Apr;95(2):203-8. doi: 10.1016/j.pbb.2010.01.006. Epub 2010 Jan 25.
Activation of NMDA receptors by glutamate is particularly important in the initial stages of memory consolidation. Memantine, a noncompetitive NMDA receptor antagonist, ameliorates memory impairment under certain circumstances, despite blocking the activation of NMDA receptors. The present experiments tested the hypothesis that memantine can improve memory deficits induced by isolation stress in day-old chicks (Gallus gallus domesticus) trained in a one-trial taste-avoidance task. Three experiments assessed the effects of memantine at different concentrations and in combination with isolation stress. The results of Experiment 1 indicate that, under normal, non-stressed conditions, memory in control animals is strong and 15.0 mM memantine impairs memory, similar to that seen in many studies of the effects of NMDA receptor antagonists on learning. However, the results of Experiments 2 and 3 showed that, when chicks were exposed to isolation stress during the pre-training period, memory formation for saline-injected control animals was impaired and 5.0 mM memantine significantly improved memory in an inverted U-shaped dose response function. The current results extend the findings that memantine can ameliorate memory impairment and supports the hypothesis that memantine, despite its action to reduce NMDA receptor activity, can facilitate normalized memory acquisition.
谷氨酸对 NMDA 受体的激活在记忆巩固的初始阶段尤为重要。美金刚是一种非竞争性 NMDA 受体拮抗剂，尽管它可以阻断 NMDA 受体的激活，但在某些情况下可以改善记忆障碍。本实验检验了以下假设：美金刚可以改善在一次性味觉回避任务中训练的 1 日龄小鸡（Gallus gallus domesticus）的隔离应激引起的记忆缺陷。三项实验评估了不同浓度的美金刚以及与隔离应激联合使用的效果。实验 1 的结果表明，在正常、无压力的情况下，对照组动物的记忆能力很强，15.0 mM 的美金刚会损害记忆，这与许多 NMDA 受体拮抗剂对学习影响的研究结果相似。然而，实验 2 和实验 3 的结果表明，当小鸡在预训练期间暴露于隔离应激时，接受盐水注射的对照组动物的记忆形成受损，而 5.0 mM 的美金刚以倒 U 形剂量反应函数显著改善了记忆。目前的结果扩展了美金刚可以改善记忆障碍的发现，并支持了以下假设：尽管美金刚可以降低 NMDA 受体活性，但它可以促进正常记忆的获得。
