孟鲁司特对东莨菪碱模型小鼠学习记忆及脑内胆碱能神经的影响

Effects of montelukast on learning memory and cholinergic system in model mice induced by scopolamine

目的:研究孟鲁司特(Mon)对东莨菪碱(Scop)致痴呆模型小鼠学习记忆及脑内胆碱能神经的影响。方法:将动物按体重随机分为5组,正常对照组[溶媒(Veh)+Veh]、阴性对照组(Scop+Veh)、阳性对照组[Scop+多奈哌齐(Done)2.0mg/kg]、低剂量孟鲁司特组(Scop+Mon 1.0mg/kg)、高剂量孟鲁司特组(Scop+Mon 2.0mg/kg)。灌胃给药,除正常对照组腹腔注射生理盐水外,其他各组小鼠给药前30min腹腔注射东莨菪碱(1.0mg·kg-1·d-1),连续给药14d后采用Morris水迷宫和Y迷宫实验测定学习记忆功能,并测定脑海马及皮层乙酰胆碱(ACh)水平及乙酰胆碱酯酶(TChE)的活性。结果:与阴性对照组相比,孟鲁司特(1.0、2.0mg·kg-1·d-1)能显著缩短Morris水迷宫隐藏平台训练的潜伏期,增加动物在空间探索实验中对目标象限的搜索时间及原平台所在位置的穿越次数,增加Y迷宫实验中正确反应次数。孟鲁司特还能显著降低小鼠海马及皮层乙酰胆碱酯酶活性,增加乙酰胆碱含量。结论:孟鲁司特通过抑制东莨菪碱所致的痴呆小鼠脑内乙酰胆碱酯酶活性增加乙酰胆碱含量,继而改善小鼠学习记忆损害。

AIM： To investigate the effects of montelukast on learning memory and cholinergic system in model mice induced by scopolamine. METHODS： Mice were randomly divided into 5 groups： vehicle plus vehicle （Veh＋Veh）, scopolamine plus vehicle（Scop＋Veh）, scopolamine plus donepezil （Scop＋Done 2. 0 mg/kg）, scopolamine plus montelukast 1.0 mg · kg^-1 · d^-1 （Seop＋Mon 1.0 mg/kg） and scopolamine plus montelukast 2.0 mg · kg^-1 · d^-1（Scop＋ Mon 2.0 mg/kg）. The drugs were intragastrically administered for 14 consecutive days at 0.5 h after intraperitoneal injection with scopolamine （1.0mg · kg^-1 · d^-1） in mice. Mice were submitted to Morris water maze （MWM） test and Y maze test. Changes in cholinergic system reactivity were also examined by measuring the aeetylcholine and acetylcholinesterase in the hippocampus and cortex. RESULTS： Scopolamine injection induced learning memory impairment in the MWMtest and Y maze test and severe decrease of cholinergic system reactivity, as indicated by reduced acetylcholine levels and increased acetylcholinesterase activity. Daily administration of montelukast significantly decreased the escape latency times to the platform during acquisition trials, increased the times in target quadrant and the number of crossing times in the probe trial, and times of correct response in Y maze test. This treatment also significantly decreased TChE activity and increased ACh levels in hippocampus and cortex. CONCLUSION： Montelukast demonstrates a significant neuroprotective effect against scopolamine-induced learning memory impairment resulting from Ach elevation through decreasing TChE activity.