Abstract: 【Abstract】〓Objective〓To evaluate the effects of LY354740 pretreatment on the learning and memory impairment induced by Ketamine in old mice. Methods〓Thirty-six healthy male C57BL/6 mice, aged 18 months, weighing 20-30 g, were randomized into 3 groups (n=12 each), ketamine group (group K), Ly354740 pretreatment group (group L), and control group (group C). In K and L groups, ketamine 30 mg/kg was injected intraperitoneally three times a day at 30-minute intervals for 2 weeks, while in group L, Ly354740 10 mg/kg was injected intraperitoneally at 30 min before the first injection of ketamine, and the group C was injected with the same dose of saline. Cognitive function was assessed using Morris water maze and open field tests after the administration of ketamine was finished. Results〓Compared with controls of group C, the animals in group K showed significantly prolonged escape latency, shortened time spent in the original platform and in the central area for the open field, likewise, the frequency of crossing the original platform was decreased (P<0.05). Compared with group K, the results above-mentioned were significantly meliorated in the Ly354740 pretreatment mice of group L (P<0.05). Conclusion〓Ly354740 pretreatment can attenuate cognitive dysfunction induced by chronic exposure to ketamine in old mice.

Key words: Ketamine, LY354740, Old mice, Cognition disorders

摘要： 【摘要】〓目的〓评价LY354740预先给药对氯胺酮暴露致老年小鼠认知功能障碍的影响。方法〓健康雄性SPF级C57BL/6小鼠36只,18月龄,体重20~30 g, 随机分成3组(n=12);氯胺酮组(K组),LY354740预处理组(L组),空白对照组(C组)。K组和L组均腹腔注射氯胺酮30 mg/kg,每隔30 min重复注射一次,每天注射氯胺酮3次,L组注射氯胺酮前30分钟注射LY354740 10 mg/kg,C组注射等量生理盐水。连续注射2周后进行认知功能测试,包括Morris水迷宫和旷场实验测试。结果〓与C组比较,K组逃避潜伏期延长,原平台停留时间和穿越平台次数减少,旷场中心区停留时间缩短;与K组比较,L组逃避潜伏期明显缩短,原平台停留时间和穿越原平台次数增多,旷场中心区停留时间延长。结论〓LY354740预先给药可以改善氯胺酮暴露所致老年鼠认知功能障碍。

关键词: 氯胺酮, LY354740, 老年鼠, 认知障碍