Differential effects of MK-801, NMDA and scopolamine on rats learning a four-member repeated acquisition paradigm.
Differential effects of MK-801, NMDA and scopolamine on rats learning a four-member repeated acquisition paradigm.
复制标题
MK-801、NMDA 和东莨菪碱对学习四人重复习得范例的大鼠的不同影响。
作者：
J. Cohn;D. Cory
谷氨酸能（NMDA）和胆碱能神经递质系统被广泛地认为是学习过程的神经化学介质。这两个系统对学习的影响可能不同；例如，尽管胆碱能拮抗剂东莨菪碱和NMDA拮抗剂MK-801都降低了大鼠在3成员重复习得范式中的总体准确性，但两种药物产生的潜在错误模式的性质明显不同：大鼠给予东莨菪碱产生跳过错误的模式，而给予MK-801主要增加了持续性错误（Cohn et al., 1992）。本实验扩展了该研究，以检验更复杂的任务，即四成员重复习得范式，是否会改变由每种药物给药引起的错误模式的性质，以及NMDA本身是否会提高重复习得范式的准确性。MK-801 （0.05-0.3mg/kg i.p.）以剂量依赖的方式显著降低了总体准确性，并且大鼠产生了类似于3成员范式的错误模式，尽管不完全相同，包括序列早期的持续性错误，以及序列后期点的额外跳过错误。MK-801显著地降低了序列中任何一点出现错误后的正确启动。NMDA （10.0-30.0mg/kg）本身不促进序列获取，即不影响总体准确性。然而，它是唯一一种增加在错误的第一或第二序列成员后正确重新启动序列的频率的药物。与MK-801一样，东莨菪碱（0.5-3.0mg/kg i.p）也会导致总体精度下降，这主要是通过增加跳过误差来实现的。然而，东莨菪碱在成功完成序列或出现错误后都不会干扰正确地重新启动序列。这些发现表明，胆碱能和谷氨酸能化合物通过不同的行为机制对学习产生影响。
The glutamatergic (NMDA) and cholinergic neurotransmitter systems have been extensively implicated as neurochemical mediators of learning processes. These two systems may differentially affect learning; for example, although both the cholinergic antagonist scopolamine and the NMDA antagonist MK-801 reduced overall accuracy of rats in a 3-member repeated acquisition paradigm, the nature of the underlying error patterns produced by the two drugs differed significantly: rats administered scopolamine produced a pattern of skipping errors, while administration of MK-801 predominantly increased perseverative errors (Cohn et al., 1992). The present experiment extended that study to examine whether a more complex task, i.e. a 4-member repeated acquisition paradigm, would alter the nature of the error patterns resulting from administration of each drug, and whether NMDA itself would increase accuracy on the repeated acquisition paradigm. MK-801 (0.05-0.3mg/kg i.p.) significantly decreased overall accuracy in a dose-dependent manner, and the rats produced a pattern of errors similar, although not identical to, that noted in the 3-member paradigm, including perseverative errors early in the sequence, but additional skipping errors at later points in the sequence. MK-801 dramatically decreased correct initiation of a sequence following an error at any point in the sequence. NMDA (10.0-30.0mg/kg) itself did not facilitate sequence acquisition, i.e. it did not affect overall accuracy. However, it was the only drug to increase the frequency of correctly reinitiating a sequence following an incorrect first or an incorrect second sequence member. Like MK-801, scopolamine (0.5-3.0mg/kg i.p.) also produced a decline in overall accuracy which was again achieved primarily through increased skipping errors. Scopolamine did not, however, interfere with correctly reinitiating a sequence either after successful completion of a sequence, or after an error. These findings suggest that cholinergic and glutamatergic compounds exert their effects on learning through different behavioral mechanisms.