Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory.
Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory.
复制标题
NMDA 受体的拮抗作用会损害嗅觉记忆的获取，但不会损害嗅觉记忆的保留。
DOI：
10.1037//0735-7044.103.1.54
复制
发表时间：
1989
影响因子：
1.9
通讯作者：
Lynch,G
中科院分区：
文献类型：
--
作者：
Staubli,U;Thibault,O;DiLorenzo,M;Lynch,G
有证据表明，N-甲基-D-天冬氨酸（NMDA）受体系统在诱导长时程增强和可能在某些类型的记忆的形成中起着关键作用，我们研究了慢性脑室内注射D-氨基膦戊酸（AP 5），一种竞争性NMDA受体拮抗剂，对嗅觉辨别和回避学习的影响。之所以选择这两项任务，是因为它们受到海马和其他富含NMDA受体的端脑结构损伤的影响程度非常不同。20只先前训练解决两种同时存在的气味之间的一系列区别的大鼠用20 mM D-AP 5或盐水（每组n= 10）输注14天。该范式的一个重要而不寻常的特征是，它允许比较药物对获得新的歧视和保留旧的歧视的影响。用AP 5处理的动物在获得具有长的试验间隔（ITIs）的低强度气味之间的辨别方面比盐水对照组犯了更多的错误。然而，当使用短ITI（< 2分钟）或强烈气味时，没有观察到缺陷。用AP 5处理的动物在识别给药前训练过的气味方面没有困难。在泵耗尽后，AP 5组的性能与对照组的性能没有区别。单向主动回避学习不受慢性灌注AP 5的影响。几种可能性进行了讨论，可以占选择性嗅觉学习赤字。我们认为，这些结果与NMDA受体参与前脑连接修饰的学习形式的假设是一致的。
Prompted by evidence pointing to a key role of the N-methyl-D-aspartate (NMDA) receptor system in the induction of long-term potentiation and possibly in the formation of some types of memory, we examined the effect of chronic intraventricular administration of D-aminophosphono-valeric acid (AP5), a competitive NMDA receptor antagonist, on olfactory discrimination and avoidance learning. These two tasks were selected because they are affected to very different degrees by damage to the hippocampus and other telencephalic structures rich in NMDA receptors. Twenty rats previously trained to solve a series of discriminations between two simultaneously presented odors were infused with either 20 mM D-AP5 or saline (n= 10 per group) for 14 days. An important and unusual feature of the paradigm was that it permitted a comparison of drug effects on acquisition of new discriminations versus retention of old ones. Animals treated with AP5 made significantly more errors than did saline controls in acquiring discriminations between low-intensity odors presented with long intertrial intervals (ITIs). However, no deficit was observed when short ITIs (< 2 min) or strong odors were used. Animals treated with AP5 had no difficulty in recognizing odors on which they were trained before administration of the drug. After exhaustion of the pumps, performance of the AP5 group was indistinguishable from that of the control group. One-way active avoidance learning was not affected by chronic infusion of AP5. Several possibilities are discussed that could account for the selective olfactory learning deficit. We propose that the results are consistent with the hypothesis that NMDA receptors are involved in those forms of learning that involve modification of connections in the forebrain.