Furusawa K
Division for Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.
Jpn J Pharmacol. 1991 Aug;56(4):483-93. doi: 10.1254/jjp.56.483.
A new task for the analysis of drug effects on the cognitive function in mice was investigated using a 4-arm maze with three selectable arms. Each trial consisted of a forced run either to the right or left arm containing a food pellet, which was changed for each trial, followed by a free-choice run after a delay (0-120 sec). The correct response was to turn to the arm 180 degrees opposite from the forced one. Entrance into the center arm in the free-choice run, which was called the non-reward response, was not reinforced at any time. As the delay became longer, correct responses decreased, but non-reward response errors remained unchanged in the well-trained mice. Without increasing the non-reward response, scopolamine and atropine, but not methylscopolamine, decreased the correct response in a delay-dependent manner at a low dose range, while diazepam did so in a delay-independent manner. Physostigmine ameliorated scopolamine-induced impairment in performance, but had less effect on the delay-induced decrease in the correct response. Other tested drugs (chlorpromazine, haloperidol, apomorphine, phentolamine, propranolol, lithium chloride, ketamine, and caffeine) had no significant effect on performance. These results suggest that CNS muscarinic blockades and diazepam treatment selectively attenuate working memory in different ways.
利用一个有三个可选臂的四臂迷宫，研究了一项分析药物对小鼠认知功能影响的新任务。每次试验包括一次强制奔跑，要么跑向包含食物颗粒的右臂，要么跑向左臂，每次试验食物颗粒的位置会改变，随后经过一段延迟（0 - 120秒）后进行自由选择奔跑。正确的反应是转向与强制奔跑方向相反180度的臂。在自由选择奔跑中进入中心臂，即所谓的无奖励反应，在任何时候都不会得到强化。随着延迟时间变长，在训练有素的小鼠中，正确反应减少，但无奖励反应错误保持不变。在不增加无奖励反应的情况下，东莨菪碱和阿托品，但不是甲基东莨菪碱，在低剂量范围内以延迟依赖的方式降低正确反应，而地西泮则以延迟独立的方式降低正确反应。毒扁豆碱改善了东莨菪碱引起的行为损伤，但对延迟引起的正确反应减少影响较小。其他测试药物（氯丙嗪、氟哌啶醇、阿扑吗啡、酚妥拉明、普萘洛尔、氯化锂、氯胺酮和咖啡因）对行为没有显著影响。这些结果表明，中枢神经系统毒蕈碱阻断和地西泮治疗以不同方式选择性地减弱工作记忆。
