慢性应激刺激对抑郁模型小鼠构建的行为学研究

Study of chronic stress stimulation on behavior of depression model mice

[目的]探讨慢性轻度不可预知应激(CUMS)结合孤养动物模型的评价指标在构建抑郁动物模型中的作用及其在抗抑郁治疗中的意义.[方法]取昆明种小鼠随机分为正常对照组、模型对照组(CUMS)及阳性对照(CUMS+氟西汀10mg/kg)组,给予小鼠35d的CUMS及孤养构建CUMS抑郁模型,通过观察抑郁小鼠模型构建过程中旷场行为、体质量及体温变化,推测抑郁模型小鼠的成模时间及适当的实验周期.[结果]旷场实验结果显示,抑郁小鼠模型构建第28d时,与正常对照组比较,模型对照组小鼠正常水平活动及垂直活动明显减少(P<0.05),提示此时构建模型成功.构建模型第35d时,模型对照组小鼠正常水平活动及垂直活动亦较对照组明显减少(P<0.05,P<0.01),提示该模型在此期间保持稳定;而阳性对照组较模型对照组水平活动及垂直活动明显增加(P<0.05,P<0.05),提示氟西汀对抑郁行为具有拮抗作用.构建模型第7,14,21,28,35d时,模型对照组体质量均明显低于正常对照组(P<0.05,P<0.01);阳性对照组实验第35d时明显逆转模型对照组体质量增长的抑制现象(P<0.05).构建模型第21,28,35d时,模型对照组体温显著低于正常对照组(P<0.01);阳性对照组实验第35d时,明显拮抗模型对照组体温降低现象(P<0.05).[结论]昆明种小鼠CUMS所致抑郁模型于实验第28d时构建成功,在28~35d期间基本稳定;可根据研究目标药物的可能作用机制、药物起效快慢或疗程来确定CUMS周期和适宜的给药时间.

OBJECTIVETo investigate the effects of chronic unpredictable mild stress（CUMS）combined with evaluation index of solitary raised animal model on building depression animal model and the significance on antidepressant treatment.METHODS Kunming mice were randomly divided into control,model control（CUMS）and positive control（CUMS plus fluoxetine 10mg/kg）group.The mice were given CUMS and raised solitary for 35 days to build CUMS depression model.Open-field behavior,body mass and body temperature were observed to speculate the modeling time and appropriate experimental cycle of depression model mice.RESULTSThe open-field behavior results showed that the normal horizontal and vertical activities of the model control group were significantly reduced on the 28 th day as compared with the control group（P〈0.05）,it hinted the success of the model building.On the 35 th day,the normal horizontal and vertical activities of the model control group were significantly decreased as compared with the control group（P〈0.05,P〈0.01）,it indicated that the model was stable during this time;while the horizontal and vertical activities of the positive control group were markedly increased as compared with the model control group（P〈0.05,P〈0.01）,it indicated that fluoxetine was antagonistic to depressive behavior.Compared with the control group,body mass of the model control group was significantly reduced on the 7th,14 th,21th,28 th,35th day（P〈0.05,P〈0.01）.The positive control group significantly reversed the inhibition of the model control group on mice increasing body mass on the 35 th day（P〈0.05）.The body temperature of the model control group was significantly lower than that in the control group on the 21 th,28th,35 th day（P〈0.01）,and the positive control group significantly reversed the hypothermia phenomenon of the model control group on the 35 th day（P〈0.05）.CONCLUSION Kunming mice depression model induced by CUMS was successfully constructed on the 28 th day,and it is basically stable during 28-35 d.The CUMS cycle and appropriate drug administration time could be determined according to the possible mechanism of the target drug.