To explore the conditions for inducing depression in C57BL/6N mice by chronic unpredictable mild stress (CUMS),observe the behavioral changes of the model mice at different time points,and evaluate and optimize the model.Methods:Depression was induced in C57BL/6N mice by CUMS (8 weeks).The changes of depression-like behaviors of mice were observed based on the sucrose preference test (SPT),open field test (OFT),forced swim test (FST),and tail suspension test (TST) at the 3rd,5th,and 8th weeks of modeling.Results:Compared with the control group,mice in the CUMS group showed poor conditions at each time point,as manifested by the hair loss,emaciation,reduced activity,etc.At the 3rd,5th,and 8th weeks,the model group demonstrated low sucrose preference percentage,long immobility time in FST and TST,and the few vertical movements in OFT,suggesting anhedonia,despair,and decreased ability of exploration.After 8 weeks of modeling,the total horizontal distance traveled decreased and the movement became slow in OFT in the model group,an indicative of decreased spontaneous motor ability of mice in CUMS group.Conclusion:CUMS is applicable to the depression modeling with C57BL/6N mice,and the depression aggravates gradually over time.