LY354740改善氯胺酮暴露引起青春期C57BL/6小鼠的空间学习记忆功能损害与焦虑

LY354740 attenuates the impairment on spatial learning and memory function and anxiety level induced by ketamine exposure in adolescent C57BL/6 mice

目的:评价LY354740预先给药对氯胺酮暴露致青春期C57BL/6小鼠的空间学习记忆功能损害及焦虑水平改变的改善作用.方法:健康雌性SPF级C57BL/6小鼠39只,6~8周龄,体质量(20±5)g,随机分成氯胺酮组(K组)、LY354740预处理组(L组)及空白对照组(C组)等3组(n=13).K组和L组均腹腔注射质量分数为30 mg/kg氯胺酮,每隔30min重复注射1次,每天注射氯胺酮3次,L组注射氯胺酮前30 min注射质量分数为10 mg/kg LY354740,C组注射等量生理盐水.第1天注射结束30 min后取新鲜海马组织测定谷氨酸质量分数(n=3).连续注射2周后进行行为学实验检测(n=10),包括旷场实验和Morris水迷宫.结果:与C组比较,K组谷氨酸明显上升(P<0.01),旷场试验中心区活动时间缩短(P<0.01),进入中心区频次减少(P<0.01),在水迷宫测试中定位航行测试逃避潜伏期延长(P<0.01),空间探索测试到达原平台潜伏期延长(P<0.01)和穿越原平台频次减少(P<0.05);与K组比较,L组旷场中心区停留时间延长(P<0.05),在水迷宫测试中定位航行测试逃避潜伏期缩短(P<0.05),空间探索测试到达原平台潜伏期缩短(P<0.01).结论:LY354740预先给药可以抑制氯胺酮诱发的海马谷氨酸增加,改善氯胺酮暴露所致青春期C57BL/6小鼠的空间学习记忆功能损害及焦虑水平上升.

Objective:To evaluate the effect of pretreatment with LY354740 on improving impairment on spatial learning and memory function and anxiety level induced by ketamine exposure in adolescent C57BL/6 mice.Methods:39 female C57BL/6 mice,aged 6~8 weeks,weighing(20±5)g,were randomized into 3 groups(n=13 per group),including Ketamine(K),LY354740(L)and control group(C).The mice in group K and L were injected intraperitoneally with ketamine(30 mg/kg)3 times a day at an interval of 30 min between each injection.The mice in group L were pretreated with LY354740(10 mg/kg)30 min before ketamine injection.Same volume of saline was injected to mice in group C.30 min after the first day of administration,fresh hippocampi(n=3)was harvested to measure glutamate content.After 2 week administration,behavioral tests including open field test and Morris water maze test were performed to evaluate cognitive function.Results:Compared with group C,group K showed higher glutamate content(P<0.01),decreased duration and frequency in central area(P<0.01)in open field test,prolonged latency to the platform in navigation test(P<0.01),and reduced first latency and frequency to original platform area in spatial exploration test(P<0.05).While compared with group K,group L showed prolonged duration in central area(P<0.05),shortened latency to the platform in navigation test(P<0.05),and decreased first latency to original platform area(P<0.01).Conclusion:Pretreatment with LY354740 can inhibit ketamine-induced glutamate increase in hippocampus,and attenuate the impairment on spatial learning and memory function and increased anxiety level induced by ketamine exposure in adolescent C57BL/6 mice.