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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.

Drug Effects on Cognitive Function in Mice Determined by the Non-Matching to Sample Task Using a 4-Arm Maze.