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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 evaluate the animal model of acquired helpless depression using ICR mice. Methods The shuttle-conditioned reflex system controlled by computer program was used to induce the non-evasive somatic trauma (IS) induction of ICR mice 360 times a day for 4 consecutive days. Each electric shock lasted for 2 s, with an average interval of 8 s and a current intensity of 0.3 mA. After screening by shuttle box avoidance procedure, the mice in the shock induction group were divided into model group (IS group, intragastric administration of solvent for 5 consecutive days, once / d) and fluoxetine treatment group (FLU group, intragastric administration of 10 mg / kg for 5 consecutive days, once / d). After induction training, the escape avoidance frequency and avoidance latency of mice were determined by delayed evasive behavioral testing program for 4 consecutive days. Results On the 2nd, 4th and 8th days after induction training, the number of escape failures in IS group increased significantly compared with non-shock (NIS) group. From the second to the fifth day after induction training, compared with the IS group, the number of escape failures in the FLU group was significantly reduced, and the escape latency was significantly shortened. Conclusion The improved model of ICR mice can be used to establish a stable animal model of acquired helpless depression and provide a reliable behavioral method for the pharmacodynamic study of antidepressants.