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利用斑马鱼建立成瘾性药物对运动机能及认知功能影响的评价模型 被引量:6

Zebrafish as a model system for assessing effects of addictive drugs on locomotor activity and cognitive performance
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摘要 目的利用斑马鱼这一新型模式动物,建立斑马鱼自发活动及学习记忆模型,并考察成瘾性药物对模型的影响。方法本实验以吗啡及甲基苯丙胺作为受试药物,利用斑马鱼行为视频跟踪分析系统自动记录动物行为参数,在自发活动模型主要测试运动路程、穿越次数及在顶部停留时间等行为,而进入营养富集区(EC区)的潜伏时间与总停留时间则作为T迷宫模型建立的主要指标,分别考察斑马鱼在运动机能及认知功能方面的行为变化。结果与正常组相比,6min内吗啡预处理组中斑马鱼运动路程、垂直穿越次数及在上部的停留时间均明显增加(P<0.05),甲基苯丙胺预处理组的垂直穿越次数及在上部的停留时间有明显的下调(P<0.01,P<0.01),提示吗啡短时暴露使斑马鱼活动性增强,甲基苯丙胺急性处理使得斑马鱼处于焦虑状态;在T迷宫测试中,正常的斑马鱼随着训练次数增加,与首次测试相比进入营养富集区(EC区)的时间有下降趋势,在EC区的停留时间明显增加(P<0.05),而与正常组相比,吗啡重复处理组中斑马鱼在EC区的停留时间无变化,而甲基苯丙胺重复处理组斑马鱼的空间学习记忆能力明显受到影响。结论成瘾性药物影响斑马鱼游泳行为与认知功能,且不同药物产生特征性影响,表明所建立模型的可靠性,可为药物引发的神经精神障碍及损伤提供快速有效的技术平台。 Aim To establish several behavioral models to char- acterize the spontaneous activity and learning ability in which zebrafish was utilized as a model animal, and then to investigate the effects of addictive drugs on these models. Methods With the video record and track system, the behavior could be recorded and quantified automatically. In the experiments, the total travel distances, entries in top zone and the top/total time spent were selected as indices in locomotor model ; the latency to the enriched chamber ( EC ) and the total time in EC were measured in T maze test. Morphine and methamphetamine ( METH ) were chosen as experimental challenges. Results In spontaneous activity test, compared to the normal group, acute morphine-trea- ted zebrafish exhibited significant increased travel distance, vertical transitions and top time ( P 〈 O. 05 ) over 6 min ; acute expo- sure of zebrafish to methamphetamine made transitions and top time decrease significantly(P 〈 O. 01, P 〈 0. 01 ). These results indicated morphine exposure induced hyperlocomotion, and acute methamphetamine produced robust anxiogenic effects. In T- maze test, there was a trend for normal fish to reduce the time that it took for them to reach the EC and to increase the time spent in the EC during the training period. In the group of mor- phine repeated exposure, the total time in EC had no signifi- cance during the training, and in the METH repeat-treated group, the space recognition ability was impaired severely. Con- clusions Addictive drug treatments have effects on the motor behavior and cognition function of zebrafish. Exposed the drugs, the zebrafish exhibits characterized behavioral phenotype; the information collected from zebrafish consists with the results obtained from mice model. It suggests that zebrafish as a reliable, inexpensive model can be used as platform for assessment of neuropsyehiatric disorders or injury.
作者 颜慧 宫泽辉
出处 《中国药理学通报》 CAS CSCD 北大核心 2012年第8期1173-1177,共5页 Chinese Pharmacological Bulletin
基金 国家科技重大专项资助(No 2009ZX09301-002 2012ZX09301003-001-006)
关键词 斑马鱼 行为模型 成瘾性药物 自发活动 认知能力 神经精神障碍 zebrafish behavioral m0del addictive drug spon- taneous activity cognitive ability neuropsychiatric disorders
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