Dennes R P, Barnes J C
Neuropharmacology Department, Glaxo Group Research Ltd, Ware, Hertfordshire, UK.
Psychopharmacology (Berl). 1993;111(4):435-41. doi: 10.1007/BF02253533.
The effects of cholinomimetic and non-cholinomimetic agents on spatial memory using a novel task in the 12-arm radial maze were investigated. The task was designed to reduce the tendency to use non-spatial strategies. Animals were repeatedly trained to retrieve food rewards from three arms, until a criterion level of performance was reached. Scopolamine (0.03 and 0.1 mg/kg SC), but not N-methylscopolamine (0.1 mg/kg SC) disrupted performance of this task. Physostigmine (0.3 mg/kg SC) and pilocarpine (30 mg/kg SC) completely reversed the deficit of performance produced by scopolamine. Furthermore, the ACE inhibitor Hoe 288 (10 nmol ICV) and the angiotensin AT1 receptor antagonist losartan (10 mg/kg SC) also significantly attenuated the scopolamine-induced deficit. These results show that this novel task in the radial maze is sensitive to the disruptive effects of scopolamine and can identify cognitive enhancing effects of both cholinomimetic and non-cholinomimetic drugs. Thus, this maze task provides a useful model for the evaluation of novel cognitive enhancing agents.
使用十二臂放射状迷宫中的一项新任务,研究了拟胆碱药和非拟胆碱药对空间记忆的影响。该任务旨在减少使用非空间策略的倾向。动物被反复训练从三个臂中获取食物奖励,直到达到标准的表现水平。东莨菪碱(0.03和0.1毫克/千克,皮下注射),但不是N-甲基东莨菪碱(0.1毫克/千克,皮下注射)会干扰这项任务的表现。毒扁豆碱(0.3毫克/千克,皮下注射)和毛果芸香碱(30毫克/千克,皮下注射)完全逆转了东莨菪碱产生的表现缺陷。此外,血管紧张素转换酶抑制剂Hoe 288(10纳摩尔,脑室内注射)和血管紧张素AT1受体拮抗剂氯沙坦(10毫克/千克,皮下注射)也显著减轻了东莨菪碱诱导的缺陷。这些结果表明,放射状迷宫中的这项新任务对东莨菪碱的破坏作用敏感,并且可以识别拟胆碱药和非拟胆碱药的认知增强作用。因此,这个迷宫任务为评估新型认知增强剂提供了一个有用的模型。