Levin E D, McGurk S R, South D, Butcher L L
Department of Psychology, University of California, Los Angeles 90024-1563.
Behav Neural Biol. 1989 Mar;51(2):270-7. doi: 10.1016/s0163-1047(89)90917-5.
Acetylcholine (ACh) systems have been found to be crucial for the maintenance of accurate cognitive performance. A great variety of studies have shown that the muscarinic ACh receptor blocker scopolamine impairs choice accuracy in the radial-arm maze. Recently, it has been found that the nicotinic ACh receptor blocker mecamylamine also impairs radial-arm maze choice accuracy. In the present study, we investigated the effects of combined administration of these two ACh blockers. Scopolamine (0.15 mg/kg) and mecamylamine (10 mg/kg) each moderately impaired choice accuracy. Combined treatment with scopolamine and mecamylamine significantly decreased choice accuracy relative to either drug alone. This combination treatment lowered choice accuracy to chance levels. These data show that nicotinic and muscarinic blockade have at least additive effects in producing an anterograde memory deficit. Concurrent blockade of these two components of ACh systems may provide a better animal model of cognitive impairments due to the loss of cholinergic neurons, such as Alzheimer's disease.
已发现乙酰胆碱（ACh）系统对于维持准确的认知表现至关重要。大量研究表明，毒蕈碱型ACh受体阻滞剂东莨菪碱会损害放射状臂迷宫中的选择准确性。最近，已发现烟碱型ACh受体阻滞剂美加明也会损害放射状臂迷宫的选择准确性。在本研究中，我们研究了这两种ACh阻滞剂联合给药的效果。东莨菪碱（0.15mg/kg）和美加明（10mg/kg）各自中度损害了选择准确性。与单独使用任一药物相比，东莨菪碱和美加明联合治疗显著降低了选择准确性。这种联合治疗将选择准确性降低到了随机水平。这些数据表明，烟碱型和毒蕈碱型阻断在产生顺行性记忆缺陷方面至少具有相加作用。同时阻断ACh系统的这两个成分可能会提供一个更好的因胆碱能神经元丧失导致认知障碍的动物模型，如阿尔茨海默病。
