Packard M G, Regenold W, Quirion R, White N M
Department of Psychology, McGill University, Montreal, Que., Canada.
Brain Res. 1990 Jul 30;524(1):72-6. doi: 10.1016/0006-8993(90)90493-u.
The present study examined the effect of systemic post-training administration of the acetylcholine muscarinic M2 receptor antagonist AF-DX 116 on the acquisition of two 8-arm radial maze tasks. On a win-stay visual discrimination task, a light cue signalled the location of food in 4 randomly selected maze arms, and rats were required to visit each of the 4 lit arms twice within a trial. Rats were given one trial per day and injected immediately post-training on day 5. AF-DX 116 (0.5 and 1.0 mg/kg) significantly improved win-stay acquisition relative to vehicle-injected controls. On a win-shift task, rats were allowed to visit 4 randomly selected maze arms, followed by a delay period. After the delay, rats were returned to the maze for a retention test in which only those 4 arms not visited prior to the delay contained food. On the test (i.e. drug) trial, rats were removed from the maze after the first 4 choices and injected with AF-DX 116 or vehicle. The retention test was given following an 18 h delay. AF-DX 116 (2.0 mg/kg) significantly improved retention relative to vehicle controls. When the injections were given 2 h post-training, no effect on retention was observed in either task. The results demonstrate that post-training injection of the selective M2 receptor antagonist AF-DX 116 improves memory in a time-dependent manner. The findings may have implications for the cholinergic pharmacotherapy of Alzheimer's disease.
本研究考察了全身性给予毒蕈碱型M2受体拮抗剂AF-DX 116对两项八臂放射状迷宫任务习得的影响。在一项“赢则停留”视觉辨别任务中，一个光信号提示食物位于4个随机选择的迷宫臂中，大鼠需要在一次试验中访问这4个有灯光的臂各两次。大鼠每天进行一次试验，并在第5天训练后立即注射药物。与注射赋形剂的对照组相比，AF-DX 116（0.5和1.0毫克/千克）显著改善了“赢则停留”任务的习得。在一项“赢则转换”任务中，大鼠被允许访问4个随机选择的迷宫臂，随后有一个延迟期。延迟后，大鼠被放回迷宫进行记忆测试，其中只有延迟前未访问过的4个臂中有食物。在测试（即药物）试验中，大鼠在前4次选择后从迷宫中取出，并注射AF-DX 116或赋形剂。在延迟18小时后进行记忆测试。与赋形剂对照组相比，AF-DX 116（2.0毫克/千克）显著改善了记忆。当在训练后2小时注射时，在两项任务中均未观察到对记忆的影响。结果表明，训练后注射选择性M2受体拮抗剂AF-DX 116能以时间依赖的方式改善记忆。这些发现可能对阿尔茨海默病的胆碱能药物治疗有启示意义。
