MK-801对大鼠行为学及认知功能的影响

Effect of MK-801 on Behavior and Cognitive Function in Rats

目的观察非竞争性NMDA受体拮抗剂地卓西平马来酸盐(MK-801)对大鼠的行为活动和认知功能的影响。方法实验组连续2周腹腔注射MK-801,对照组注射等容量生理盐水。分别评估注射后第1、5、10、14天大鼠的行为学改变;停药后第1、2、3、4天与停药后第12、13、14、15天分别进行Morris水迷宫实验,比较两组的定位航行和空间探索时间。结果两组动物的运动量、共济失调、刻板行为评分均实验组高于对照组;停药后第1、2、3天,实验组大鼠逃逸时间高于对照组(P<0.01),停药后第12、13、14天变化无统计学意义(P>0.05);实验组大鼠在停药第4天空间探索时间低于对照组(P<0.01),同时也低于停药后第15天(P<0.01);第15天实验组与对照组之间的停留时间差异无统计学意义(P>0.05)。结纶MK-801可诱发大鼠出现精神分裂症症状,且可致使大鼠的学习记忆功能下降,但此影响并非不可逆的。

Objective To observe the effect of dizocipine maleate（MK-801）,a selective non-competitive N-methy1D-aspartate（NMDA） receptor antagonist,on behavior and cognitive function in rats.Methods The rats in experimental group were intraperitoneally injected with MK-801,and the control group rats were intraperitoneally injected with the same dose of saline for 14 days.The behavioral assessment was done after treatment at the 1st,5th,10th,14th day respectively.After drug withdrawal at the 1st,2nd,3rd,4th days and 12th,13th,14th,15th days respectively,Morris watermaze was used to compare the time of place navigation trials and spatial probe trials.Results The scores of locomotion distance,ataxia and stereotype behavior were significantly higher in experimental group than that of control group.After drug withdrawal at the 1st,2nd,3rd days,the escape latency was significantly higher in experimental group than that of control group（P0.01）.There were no significant difference after drug withdrawal at the 12th,13th,14thdays（P0.05）.Retention time of spatial probe trials was significantly shorter at 4 days after withdrawal of drug at in experimental rats than that of control group（P0.01）.It was significantly shorter after drug withdrawal at the 4th day than that of the 15th day in experimental rats（P0.01）,and there was no significant difference after drug withdrawal at the 15th day between two groups（P0.05）.Conclusion MK-801 could successfully induce Schizophrenia-like behavior in SD rats and cause short-term learning and memory capability reduction,but the effect was not irreversible.