Fig. 1: Repeated short-term mild stress reversed stress-induced depressive and social behavioral impairments.

a Experimental design. Young mice (2 months, 2 M) subjected to CRST were treated with repeated 5-min restraint (RS5) or imipramine (IMI, 20 mg/kg, intraperitoneally (i.p.)) for 14 days (n = 6 animals per group). b–d Basal serum GC levels (b), adrenal gland weights (c) and CRH and AVP levels in the PVN (d) for the indicated groups. e–l Immobility time (s) in the TST (e) and FST (f). Social behavior tests: locomotor activity during habituation (g); heatmaps showing exploring activity (h); interaction time (i) with a target versus an empty in the SIT; and interaction time with familiar versus novel targets in the SMT at 5 min (j), 1 h (k) and 24 h (l) post-SIT for the indicated groups. m Experimental design. Young (2 M) and aged (14.5 months, 14.5 M) mice were subjected to 7-day 2-h restraint (RST7d) and subsequently with repeated 5-min restraint (RS5) for 14 days (n = 6 animals per group). n–p Basal serum GC levels (n), adrenal gland weights (o) and CRH and AVP levels in the PVN (p) for the indicated groups. q–w The immobility time in the TST (q) and FST (r). Sociability tests: the locomotion during habituation (s); interaction time (t) with a target versus an empty in the SIT; and interaction time with familiar versus novel targets in the SMT at 5 min (u), 1 h (v) and 24 h (w) post-SIT for the indicated groups. Data are mean ± s.e.m. *,**, difference between indicated groups. *P < 0.05; **P < 0.01 (Student’s t-test; one-way ANOVA followed by Newman–Keuls post-hoc test). See Supplementary Data 4 for statistical details.