小鼠获得性无助抑郁模型的优化与评价  

Optimization and evaluation of learned helplessness in mice as a model of depression

作　　者：赵楠[1] 安磊[2] 张有志[1] 王真真[1] 李云峰[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]大连医科大学药学院,辽宁大连116044

出　　处：《军事医学》2013年第6期439-442,共4页Military Medical Sciences

基　　金：国家科技重大专项资助项目(2012ZX09J12201-004);国家自然科学基金资助项目(81202507;81173036;81072624;81001653)

摘　　要：目的利用ICR小鼠改进获得性无助抑郁动物模型并对其进行评价。方法采用电脑程序控制的穿梭箱条件反射系统,每天360次、连续4 d给予ICR小鼠不可逃避性足底电击(IS)诱导训练,每次电击持续2 s,平均间歇8 s,电流强度0.3 mA。经过穿梭箱回避程序筛选,将电击诱导组小鼠分为模型组(IS组,灌胃给予溶剂,连续5 d,1次/d)和氟西汀治疗组(FLU组,灌胃剂量10 mg/kg,连续5 d,1次/d)。诱导训练后,连续4 d采用延迟的逃避行为测试程序测定小鼠的逃避失败次数和逃避潜伏期。结果诱导训练后第2、4、8天,与非电击(NIS)组比较,IS组逃避失败次数均显著增加。在诱导训练后第2～5天,与IS组比较,FLU组逃避失败次数显著减少,逃避潜伏期显著缩短。结论通过改进措施,利用ICR小鼠可建立稳定的获得性无助抑郁动物模型,为抗抑郁药物药效学研究提供可靠的行为学方法。Objective To improve and assess the learned helplessness（LH） in ICR mice as a model of depression.Methods Using the shuttle-box conditioned response system controlled by the computer,ICR mice were exposed to 360 inescapable foot-shock（IS） training trails（each of 0.3 mA amplitude and 2 s duration on a 8 s variable inter-trial interval） per day for four consecutive days.After IS training trails,the mice were screened by shuttle-box avoidance program and assigned to model group（IS,vehicle,ig,once daily for 5 days） and fluoxetine treatment group（FLU,10 mg/kg,ig,once daily for 5 days）.The number of escape failure（EF） and the escape latency（EL） were detected by a delayed escape response program for four consecutive days after IS training trails.Results Compared with non-inescapable shock（NIS） group,EF in IS group was increased significantly on d 2,4 and 8 after IS training trails.Compared with IS group,EF in FLU group was decreased significantly while EL in FLU group was shortened significantly.Conclusion ICR mice can be used to establish the learned helplessness as a model of depression through appropriate optimization,which can provide a reliable behavior method for the antidepressant efficacy study.

关 键 词：抑郁动物模型 获得性无助 ICR小鼠 穿梭箱逃避反应 氟西汀 

分 类 号：R-332[医药卫生]