Griesbach G S, Amsel A
Department of Psychology and Institute for Neuroscience, University of Texas, Austin, TX 78712, USA.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11435-9. doi: 10.1073/pnas.95.19.11435.
These experiments observed the immediate and long-term effects of neonatal treatment with MK-801 on patterned single alternation (PSA), a form of nonspatial, memory-based learning. Rat pups were injected daily on postnatal days (PND) 7-19, with MK-801 (MK+) or the less active isomer of MK-801 (MK-) (0.25 mg/kg), and trained at either PND 22 or 60. Rats treated with MK+ or MK- and trained on PND 22 were significantly impaired in PSA when compared with the saline control. Beyond the learning impairment, MK+ rats showed an overall decreased running speed during training. They also presented an array of abnormal behaviors and significant weight loss. These nonassociative variables were determined for several doses (0.025, 0. 05, 0.1, 0.15, and 0.20 mg/kg) through PND days 22-25. Rats that received the threshold dose for secondary effects (0.025 mg/kg) also showed an overall decrease in running speed, but failed to show a significant nonspatial learning impairment on PSA. The PSA learning impairment was found to be not long lasting; rats trained at PND 60, after neonatally receiving the original high dose of MK-801, did not differ from controls.
这些实验观察了新生大鼠用MK-801治疗对模式化单交替（PSA）的即时和长期影响，PSA是一种基于记忆的非空间学习形式。在出生后第7至19天（PND），每天给幼鼠注射MK-801（MK+）或活性较低的MK-801异构体（MK-）（0.25mg/kg），并在PND 22或60进行训练。与生理盐水对照组相比，在PND 22接受MK+或MK-治疗并训练的大鼠在PSA方面明显受损。除了学习障碍外，MK+大鼠在训练期间的整体奔跑速度下降。它们还表现出一系列异常行为和显著的体重减轻。在PND 22至25期间，对几种剂量（0.025、0.05、0.1、0.15和0.20mg/kg）测定了这些非联想变量。接受次要效应阈值剂量（0.025mg/kg）的大鼠也表现出整体奔跑速度下降，但在PSA上未表现出明显的非空间学习障碍。发现PSA学习障碍并非持久；新生大鼠接受原始高剂量MK-801后，在PND 60训练的大鼠与对照组没有差异。
