抗精神病药对小鼠空间记忆的影响

Effects of antipsychotic drugs on spatial memory in mice

目的:考察抗精神病药氟哌啶醇、氯氮平、奥氮平对小鼠空间记忆影响。方法:实验于2003-11/2004-07在沈阳药科大学药学院神经药理实验室完成。选择健康雄性昆明种小鼠240只。①在测定游泳能力的实验中,每40只小鼠随机分为3组:氯氮平组、奥氮平组、氟哌啶醇组。受试药氯氮平分为0.1mg/kg,0.3mg/kg,1mg/kg剂量组及空白对照组,每组10只;奥氮平和氟哌啶醇均分为0.01mg/kg,0.03mg/kg,0.1mg/kg剂量组及空白对照组。每只小鼠皮下给药50min后,放入游泳能力测定装置中,从起始一端入水,记录小鼠从入水到爬上对面终点平台的游泳时间。②在Morris水迷宫实验中,分组同小鼠游泳能力实验。小鼠每天给药后50min进行训练,连续给药5d。在训练过程中,每只小鼠每天连续训练4次,连续进行5d。训练时,分别从4个端点(每个点每天只能使用1次)将小鼠面向池壁放入水中。记录每只鼠分别从4个端点入水开始到找到水下平台所需时间(逃避到平台上的潜伏期),此为学习成绩。若小鼠在60s内未找到平台,实验者将其放在平台上,停留20s,潜伏期按60s计算。每次训练间隔20s。4次潜伏期的算术平均值作为这一时间段的成绩,参与最终结果统计。结果:240只小鼠均进入结果分析。①在游泳能力测定实验中,与空白对照组比较,0.01～0.1mg/kg氟哌啶醇,0.1～1mg/kg氯氮平及0.01～0.1mg/kg奥氮平对小鼠游泳时间无明显影响,也未见对小鼠游泳姿态、爬上平台能力有明显影响。②在Morris水迷宫实验中,连续测定5d的结果表明,与空白对照组比较,氟哌啶醇0.1mg/kg在第5天明显延长小鼠找到平台的时间;氯氮平0.3mg/kg在第4天明显延长小鼠找到平台的时间;氯氮平1mg/kg在第1,3,4,5天明显延长小鼠找到平台的时间;奥氮平0.1mg/kg在第3,5天明显缩短小鼠找到平台的时间。结论:氟哌啶醇和氯氮平在不同程度上对小鼠的空间记忆有损伤作用,而奥氮平对小鼠的空间记忆有改善作用。

AIM： To investigate the effects of antipsychotic drugs haloperidol, clozapine and olanzapine on the spatial memory in mice. METHODS： The experiment was carried out in the laboratory of Neuropharmacology, Department of Pharmacology, Shenyang Pharmaceutical University from November 2003 to July 2004. Totally 240 healthy male Kunming mice were adopted in this study. ①Swimming ability test： Every forty mice were randomly divided into 4 groups （n=10）： one control group and three drug groups. The effects of haloperidol, clozapine and olanzapine on swimming speed in mice were investigated. The tests started 50 minutes after subcutaneous administrations of haloperidol （0.01, 0.03 or 0.1 mg/kg）, clozapine （0.1, 0.3 or 1 mg/kg）, olanzapine （0.01, 0.03 or 0.1 mg/kg） or vehicle. During the test, the mouse was put into the water at the starting point. The swimming time from the starting point to the end of the pool was recorded. ②Morris water maze test： Every forty mice were assigned as above. The trial started 50 minutes after subcutaneous administrations of haloperidol （0.01, 0.03 or 0.1 mg/kg）, clozapine （0.1, 0.3 or 1 mg/kg）, olanzapine （0.01, 0.03 or 0.1 mg/kg） or vehicle to mice everyday continuously for 5 days. Each mouse was trained four times daily for five consecutive days. During the training, each mouse was placed by hand into the water facing the wall of the circular pool, at four equally spaced points around the edge of the pool （once a day for each point）. The swimming time from entering the water to reach the hidden platform （the escape latency） was recorded as the learning result. If the platform was not found within 60 seconds, the mouse was manually placed onto the platform and given a maximum score of 60 seconds. After reaching the platform, all .the mice were allowed to remain on it for 20 seconds. The escaping latencies of each mouse for four times daily were recorded and the mean escaping latency was calculated. RESULTS： Totally 240 mice entered the final analysis.①In the swimming ability test, haloporidol of 0.01-0.1 mg/kg, clozapine of 0.1-1 mg/kg and olanzapine of 0.01-0.1 mg/kg all made unobvious impacts on the swimming time and pose as Well as the abilities of climbing on the platform of mice, compared with the controls.②In Morris water maze test, the haloporidol at the dose of 0.1 mg/kg caused a significant increase in the time of reaching the platform on the 5^th day. Clozapine, at the dose of 0.3 mg/kg, caused a significant increase in the time of reaching the platform on the 4^th day. Clozapine, at the dose of 1 mg/kg, caused a significant increase in the time of reaching the platform on the 1^th, 3^rd, 4^th and 5^th day. Olanzapine at the dose of 0.1 mg/kg showed a significant decrease in the time of reaching the platform on the 3^rd and 5^th day. CONCLUSION： Both haloperidol and clozapine can impair spatial memory, whereas olanzapine can improve spatial memory of mice.