多次使用咪达唑仑对小鼠记忆获得的影响

Effects of midazolam repeated administration on memory acquisition in mice

目的:观察多次使用不同剂量的咪达唑仑对小鼠记忆获得的影响。方法:实验采用避暗法和跳台法。120只昆明种小鼠分成随机区组设计,分为咪达唑仑0.5mg·kg-1(M1)组、1mg·kg-1(M2)组、2mg·kg-1(M3)组、4mg·kg-1(M4)组、阳性对照药东莨菪碱(S)组、阴性对照药生理盐水(NS)组,每组20只;各组再随机选取10只,参加跳台实验或避暗实验。M1组、M2组、M3组和M4组分别以咪达唑仑0.5,1,2,4mg·kg-1、S组以2mg·kg-1东莨菪碱、NS组以10mL·kg-1生理盐水,tid、连续腹腔注射10d后进行训练,24h后进行记忆测验,以潜伏期和错误次数作为记忆获得成绩的指标。比较不同组间的记忆成绩差异。结果:不同剂量M组与NS组相比,潜伏期缩短、错误次数增多(P<0.05);S组与NS组相比、S组与M1组相比、S组与M2组相比,均表现为潜伏期缩短、错误次数增多(P<0.05)。而M3组、M4组与S组相比,潜伏期和错误次数相似(P>0.05);M2、M3和M4组与M1组相比、M3和M4组与M2组相比,潜伏期缩短、错误次数增多(P<0.05),但M3组与M4组相比,潜伏期和错误次数相似(P>0.05)。咪达唑仑对小鼠记忆获得的抑制呈剂量依赖性。避暗实验和跳台实验结果相似。结论:咪达唑仑多次使用后可呈剂量依赖性地抑制小鼠记忆的获得。

OBJECTIVE To investigate the effects of midazolam repeated administration on memory acquisition in mice.METHODS Step-through test and step-down test were used in this experiment. 120 KM mice were divided randomly into 6 groups： group M1 ,group M2 ,group M3 ,group M4 ,group S and group NS. 20 mice in every group were randomly allocated into step-through test or step-down test, respectively. Mice in group M1, group M2, group M3 and group M4 were administrated midazolam of 0. 5,1,2,4 mg·kg^-1 by intraperitoneal injection three times per day for 10 days, respectively. As a control, mice in group S were administrated scopolamine of 2 mg·kg^-1 ,mice in group NS were administrated saline of 10 mL·kg^-1. Step-through test or step-down test was operated after 10-day-term administration finished. Memory acquisition of mice was tested 24 hours later after the training. The markers of memory acquisition based on the latencies and the numbers of errors. RESULTS Repeated administration of midazolam before the passive avoidance learning reduced the latencies and increased the numbers of errors after 24 hours. Midazolam administration resulted in a dose-dependent decrease in step-through latencies and increase in the numbers of errors. However the latencies and the numbers of errors were not statistically significant in group M3 and M4 （P 〉0. 05）. Same results were observed from both step-through and step-down test. CONCLUSION These results indicate that repeated midazolam administration impairs memory acquisition in mice by a dose-dependent manner.