幼年注射氟西汀诱导制备成年ICR小鼠抑郁模型

目的通过幼年注射氟西汀(Flu)制备成年小鼠抑郁模型,探讨其表观有效性和预测有效性。方法 幼年ICR小鼠出生后第4到第21天连续ip给予Flu 10 mg.kg-1(幼年诱导模型组),正常饲养至9周龄后,分为模型组、ig给予Flu 10 mg.kg-1和氟哌啶醇0.1 mg.kg-1组,连续3周后开始检测实验,测试期间继续给药,测试完成后小鼠为12～13周龄。开场实验检测跨格数,悬尾实验检测不动时间,明暗穿箱实验检测明暗穿箱次数。结果 与正常对照组相比,幼年诱导模型组小鼠成年后,自主活动显著减少(跨格数:83±30 vs 58±19;站立数:32±10 vs 20±8),悬尾不动时间显著延长〔83±46 vs(128±56)s〕,明暗穿箱次数显著减少(18±5 vs 10±4)。小鼠连续ig给予Flu 10 mg.kg-1后,自主活动显著增加(跨格数:58±19 vs 85±41;站立数:20±8 vs 30±12),悬尾不动时间显著缩短〔128±56 vs(71±40)s〕,明暗穿箱次数显著增加(10±4 vs 17±7),各指标均恢复至正常对照组水平;而给予氟哌啶醇0.1 mg.kg-1组小鼠,各指标数据无明显改变,同时表现出镇静作用。结论 幼年小鼠注射Flu成年后的表现符合抑郁模型表观有效性和预测有效性特征,有望成为制备更合理的抑郁症动物模型方法。

Adult ICR mice depressive model established by fluoxetine exposure at neonatal stage

OBJECTIVE To explore and establish a behavioral and pathological model for depression in ICR mice, and to evaluate its predictive validity and face validity. METHODS Neonatal ICR mice were ip given fluoxetine 10 mg·kg^-1 for 17 d (from the 4th day to 21st day after birth) and normally housed until they became adults(about 9 weeks after birth). The adult mice were ig treated with fluoxetine (Flu) 10 mg·kg^-1 or haloperidol (Hal) 0.1 mg ·kg^-1 for 3 weeks, and their behavior was measured by open-field test, tail-suspension test and light-dark transition test. RESULTS Neonatal exposure to Flu induced a ″depression-like or anxiety-like″ behavior in the adult mice, as shown by the decreased locomotor activity(crossing times: 83±30 vs 58±19; rear times: 32±10 vs 20±8), decreased light-dark transitions(18±5 vs 10±4) and increased immobility time (83±46 vs (128±56)s) in the open-field test, light-dark transition test and tail-suspension test, respectively. Chronic Flu 10 mg·kg^-1(ig) administation for 3 weeks all normalized ″depression-like or anxiety-like″ changes in behaviors: locomotor activity(crossing times: 58±19 vs 85±41; rear times: 20±8 vs 30±12) increased, immobility time (128±56 vs (71±40)s) decreased and light-dark transition times(10±4 vs 17±7) increased. However chronic treatment with Hal, a classical antipsychotics without antidepressant potential, had no such effect. CONCLUSION Neonatal exposure to Flu induces an adult depression model in ICR mice that exerts good predictive validity and face validity, and is likely very valuable potential behavioral and pathological model for depression.