Altered NMDA sensitivity and learning following chronic developmental NMDA antagonism
Altered NMDA sensitivity and learning following chronic developmental NMDA antagonism
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DOI：
10.1016/s0031-9384(97)00169-8
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发表时间：
1997-11-01
影响因子：
2.9
通讯作者：
Petit, TL
中科院分区：
文献类型：
--
作者：
Brooks, WJ;Weeks, ACW;Petit, TL
我们之前已经证明，长期给予 N-甲基-D-天冬氨酸 (NMDA) 拮抗剂会降低突触发育；然而，在退出 NMDA 拮抗作用后，会出现一个反弹期，在此期间突触发生超过对照水平。目前的研究旨在探索这一戒断期，使用非竞争性拮抗剂苯环己哌啶 (PCP)，检查与 NMDA 受体有关的 2 种行为测量：1. NMDA 诱导的癫痫发作，2. 莫里斯水迷宫中的学习和记忆。使用与之前检查突触发育相同的方案，雄性 Long-Evans 大鼠每天皮下注射 1 次 10 mg/kg PCP 或其生理盐水载体，持续 15 天，从出生后第 5 天 (P5) 开始，到 P20 结束。然后在 P21、P26、P36 或 P56 上评估动物对 NMDA 诱导的癫痫发作的敏感性，或者在 P23、P26、P30、P38 和 P75 上评估它们在莫里斯水迷宫中的采集性能和初始航向。 PCP 长期治疗导致 NMDA 给药后癫痫发作活动的行为评级更高，在最后一次注射 PCP 后 1(P21)、5(P26) 和 15(P36) 天观察到，表明在退出发育性 NMDA 拮抗作用后，在此期间 NMDA 受体/通道复合物的敏感性增加。经过 PCP 处理的动物还需要进行更多的试验才能在 P23、P26 和 P30 的莫里斯水迷宫中达到标准，并且在所有测试日中显示的初始游泳方向的准确度明显较低。研究结果根据 NMDA 受体通道复合物在发育和学习/记忆过程中的作用进行了讨论。 (C) 1997 爱思唯尔科学公司。
We have previously shown that chronic developmental administration of N-methyl-D-aspartate (NMDA) antagonists reduces synaptic development; however, on withdrawal from NMDA antagonism, there is a rebound period during which synaptogenesis exceeds control levels. The current research was undertaken to explore this period of withdrawal, using the noncompetitive antagonist phencyclidine (PCP), examining 2 behavioral measures in which the NMDA receptor is implicated: 1. NMDA-induced seizures, and 2. learning and memory in the Morris water maze. Using a protocol identical to that previously used to examine synaptic development, male Long-Evans rats were given 1 daily SC injection of either 10 mg/kg PCP or its physiological saline vehicle for a period of 15 days, beginning on postnatal Day 5 (P5) and ending on P20. Animals were then assessed for either sensitivity to NMDA-induced seizures on P21, P26, P36, or P56, or they were assessed for their acquisition performance and initial heading in the Morris water maze on P23, P26, P30, P38, and P75. Chronic treatment with PCP resulted in greater behavioral ratings of seizure activity after NMDA administration, observed 1(P21), 5 (P26), and 15 (P36) days after the last injection of PCP, indicating increased sensitivity of the NMDA receptor/channel complex during this period after withdrawal from developmental NMDA antagonism. PCP-treated animals also required significantly more trials to reach criterion in the Morris water maze on P23, P26, and P30, and displayed significantly less accurate initial swim headings on all test days. The results are discussed in terms of the role of the NMDA receptor-channel complex in development and learning/memory processes. (C) 1997 Elsevier Science Inc.