Fig. 1: 5-d UMS exposure induces depression-like behavior in mice.

a Schematic of experimental design and timeline. Representative tracks (b) and heatmaps (c) displaying mouse movement in the open field test. Total distance of movement (d), line crosses (e), rearing (f), and center entries (g) in the open field test. N = 14 and 17 mice for control and 5-d UMS groups, respectively. Two-tailed unpaired t-test: distance, t₍₂₉₎ = 1.214, p = 0.2347; line crosses, t₍₂₉₎ = 1.286, p = 0.2088; rearing, t₍₂₉₎ = 0.1964, p = 0.8457; and center entries, t₍₂₉₎ = 0.4110, p = 0.6841. The immobility time (h), climbing time (i), swimming time (j), and defecation (fecal boli) (k) in the forced swim test. N = 14 and 17 mice for control and 5-d UMS groups, respectively. Two-tailed unpaired t-test: immobility time, t₍₂₉₎ = 2.172, p = 0.0382; climbing time, t₍₂₉₎ = 2.220, p = 0.0344; swimming time, t₍₂₉₎ = 2.682, p = 0.0119; defecation, t₍₂₉₎ = 0.02498, p = 0.9802. l Graph represents sucrose preference data (%) during baseline (Day 0) and treatment (Day 7) phases of the study. N = 14 and 17 mice for control and 5-d UMS groups, respectively. Two-way ANOVA (factor 1: time; factor 2: treatment): F_{time×treatment (1, 58)} = 3.348, p = 0.0724; F_{time (1, 58)} = 0.2884, p = 0.5933; F_{treatment (1, 58)} = 13.40, p = 0.0005. Tukey’s HSD post hoc test: after treatment, p_{(control vs. 5-d UMS)} = 0.0015. m Immobility time in the tail suspension test. N = 14 and 17 mice for control and 5-d UMS groups, respectively. Two-tailed unpaired t-test: t₍₂₉₎ = 2.136, p = 0.0413. n Corticosterone levels in mouse serum (n = 5 per group). t₍₈₎ = 2.415, p = 0.0422. o Representative images showing c-Fos expression in the NAc (left, scale bar, 200 and 20 μm) and the number of c-Fos expressing neurons in NAcc and NAcs (right). N = 3 and 4 mice for control and 5-d UMS groups respectively. Two-tailed unpaired t-test: NAcc, t₍₁₉₎ = 2.097, p = 0.0496; NAcs, t₍₂₀₎ = 2.326, p = 0.0307. p Representative images showing c-Fos expression in the mPFC (left, scale bar 200 and 20 μm), and the number of c-Fos expressing neurons in Cg1, PrL, and IL (right). N = 4 and 3 mice for control and 5-d UMS groups, respectively. Two-tailed unpaired t-test: Cg1, t₍₁₇₎ = 2.738, p = 0.0140; PrL, t₍₂₂₎ = 2.405, p = 0.0250; IL, t₍₁₉₎ = 3.199, p = 0.0047. The data are expressed as mean ± s.e.m. *p < 0.05, **p < 0.01 and ***p < 0.001. 5-d UMS 5-day unpredictable mild stress, OFT open field test, FST forced swim test, TST tail suspension test, WB western blotting, co-IP co-immunoprecipitation, IHC immunohistochemistry, ELISA enzyme-linked immunosorbent assay, NAcc NAc core, NAcs NAc shell, Cg1 cingulate cortex 1, PrL prelimbic cortex, IL infralimbic cortex.