Fig. 1: Repeated treatment with short-term behavioral stress produces anti-depressive effects in stress-induced models of depression.

a Experimental design. Mice were exposed to 5-min or 2-h restraint for 14 days as depicted. CRST mice were treated for 14 days with 5-min, 10-min, or 15-min restraint or imipramine (RS5, RS10, RS15, and IMI, respectively), and they were placed in the behavioral tests. b–g Representative tracks and the % time spent in the target and nontarget fields in the two-chamber sociability test (b), the % sucrose-preference in the SPT (c), and immobility time in the TST (d) and FST (e) for the indicated groups on post-stress days 15–17. K-means clustering (k = 2) of individuals in the SIT  × SPT × [TST × FST] matrix (f) and % composition of each group in the clusters (g). PCA was used for dimension reduction of the TST × FST components (PVE, 81.3%) (n = 9–10 animals per group). h–I Immobility time in the TST (h) and FST (i) for the indicated groups on post-stress days 43 and 44 (n = 8–10 animals per group). j Experimental design. Mice subjected to CSDS were placed in the social interaction test on day 11 and susceptible and resilient groups were selected on the basis of the social interaction ratio. The susceptible mice were treated with RS5 and then were placed in the behavioral tests. k–n The % time spent in the target chamber in the two-chamber SIT (k), the % sucrose-preference in the SPT (l), and immobility time in the TST (m) and FST (n) for the indicated groups (n = 8–11 animals per group). Data were mean ± SEM. Gray circles represent individual data points. *, the difference compared to control; #, the difference compared to CRST. *, #, p < 0.05; **, ##, p < 0.01 (One-way ANOVA followed by Newman–Keuls post hoc test). See Supplementary Data 4 for statistical details.