Watanabe Y, Himi T, Saito H, Abe K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Brain Res. 1992 Jun 5;582(1):58-64. doi: 10.1016/0006-8993(92)90316-2.
The effects of 7-chlorokynurenic acid (7-Cl-Kyn), a selective antagonist at the glycine site associated with the N-methyl-D-aspartate (NMDA) receptor, on hippocampal long-term potentiation (LTP) and behavioral performances in a spatial learning task were investigated. Extracellular recordings of evoked potential (population spike) were made in rat hippocampal slices. Perfusion of 7-Cl-Kyn (10(-5) M) inhibited the induction of LTP following a tetanic stimulation (51 or 101 pulses at 100 Hz) both in the Schaffer/commissural-CA1 pyramidal cell synapses and in the perforant path-dentate granule cell synapses. Acquisition of a spatial memory in the Morris water maze was examined using rats chronically cannulated for application of drugs. The intact and vehicle-injected rats learned easily to escape onto a hidden platform with short latencies, while the rats given an injection of 7-Cl-Kyn (10(-8) mol/brain, i.c.v.) prior to every session took a longer time and a longer path to escape even after all 5 sessions of trials. Injection of 7-Cl-Kyn did not affect the swimming speed, an index of swimming ability. This is the first report providing direct evidence that endogenous glycine supports the processes of learning and memory.
研究了7-氯犬尿氨酸（7-Cl-Kyn），一种与N-甲基-D-天冬氨酸（NMDA）受体相关的甘氨酸位点的选择性拮抗剂，对海马长时程增强（LTP）和空间学习任务中行为表现的影响。在大鼠海马切片中进行诱发电位（群体峰电位）的细胞外记录。灌注7-Cl-Kyn（10^(-5) M）可抑制强直刺激（100 Hz下51或101个脉冲）后LTP在Schaffer/联合-CA1锥体细胞突触和穿通通路-齿状颗粒细胞突触中的诱导。使用长期插管用于药物给药的大鼠，在莫里斯水迷宫中检测空间记忆的获取。完整和注射赋形剂的大鼠很容易学会以短潜伏期逃到隐藏平台上，而在每次试验前注射7-Cl-Kyn（10^(-8) mol/脑，脑室内注射）的大鼠即使在所有5次试验后仍需要更长时间和更长路径才能逃脱。注射7-Cl-Kyn不影响游泳速度，游泳速度是游泳能力的一个指标。这是第一份提供直接证据表明内源性甘氨酸支持学习和记忆过程的报告。
