Cohn J, Ziriax J M, Cox C, Cory-Slechta D A
Environmental Health Sciences Center, University of Rochester School of Medicine and Dentistry, NY 14642.
Psychopharmacology (Berl). 1992;107(2-3):243-54. doi: 10.1007/BF02245144.
An understanding of the differential role of cholinergic and glutaminergic systems may be limited by the failure to move the analysis of learning impairments beyond an assessment of changes in overall accuracy. This paper reports the results of two studies in which the effects in rats of scopolamine (0.5-3.0 mg/kg IP), a cholinergic antagonist, and MK-801 (0.05-0.3 mg/kg IP), an NMDA-receptor antagonist, were compared in two different repeated learning procedures and the nature of the underlying error patterns produced by each was evaluated. The first study examined drug effects upon a repeated sequence acquisition procedure and found that while both drugs decreased overall accuracy in a dose-dependent manner, the predominant error pattern varied significantly with drug; scopolamine primarily produced skipping errors within the sequence, whereas MK-801 more prominently increased perseveration on the first and second members of the sequence. In the second study, which used a repeated transition procedure, both drugs again significantly decreased overall accuracy in a dose-dependent manner, but no consistent differences in error patterning produced by the drugs were observed. Thus, while both cholinergic and NMDA systems play a role in learning, the behavioral processes underlying the changes in overall accuracy may differ, as indicated by the differential patterns of errors produced by scopolamine and MK-801 in the repeated acquisition baseline. Furthermore, the observed differences in the underlying behavioral processes of scopolamine and MK-801 in the repeated acquisition but not on the repeated transition procedure suggest that each of the two drugs may affect more than one of the variables controlling behavior, with the relative impact of drug-related changes in controlling variables depending upon the operative contingencies of the learning task.
对胆碱能系统和谷氨酸能系统不同作用的理解，可能因未能将学习障碍的分析从整体准确性变化的评估扩展而受到限制。本文报告了两项研究的结果，其中在两种不同的重复学习程序中比较了胆碱能拮抗剂东莨菪碱（0.5 - 3.0毫克/千克腹腔注射）和NMDA受体拮抗剂MK - 801（0.05 - 0.3毫克/千克腹腔注射）对大鼠的影响，并评估了每种药物产生的潜在错误模式的性质。第一项研究考察了药物对重复序列获取程序的影响，发现虽然两种药物均以剂量依赖性方式降低了整体准确性，但主要的错误模式因药物而异；东莨菪碱主要在序列中产生跳过错误，而MK - 801更显著地增加了对序列中第一个和第二个元素的持续反应。在第二项使用重复转换程序的研究中，两种药物再次以剂量依赖性方式显著降低了整体准确性，但未观察到药物产生的错误模式有一致差异。因此，虽然胆碱能系统和NMDA系统在学习中都起作用，但如东莨菪碱和MK - 801在重复获取基线中产生的不同错误模式所示，整体准确性变化背后的行为过程可能不同。此外，在重复获取程序中观察到的东莨菪碱和MK - 801潜在行为过程的差异，而不是在重复转换程序中的差异，表明这两种药物可能影响不止一个控制行为的变量，药物相关变化在控制变量中的相对影响取决于学习任务的操作意外情况。
