Fig. 1: CSDS induces anxiety-related behaviors independently of social avoidance behavior.
a Experimental timeline for social interaction (SI) and elevated plus maze (EPM) or open field (OFT) tests. b Schematic of CSDS paradigm. c SI behavior in stress-naïve control (CTL) and socially defeated mice: AD mice display depressive-like social avoidance behavior and anxiety-like phenotype, and A mice exhibit only anxiety-like behavior (see data panels below), blue circles represent mean ± s.e.m. (Paired t-tests, n = 28 CTL t = 9.02 p = 1.22e−09, n = 39 AD t = 10.38 p = 1.27e−12, and n = 27 A mice t = 6.78 p = 3.38e−07, examined over 3 independent replicated experiments). d Resulting social interaction ratio, another way to analyze SI behavior that measures stable, relative time spent in SI zone (mean ± s.e.m., Kruskal–Wallis test, H2/91 = 67.37; Z = 6.997 p < 0.001; Z = 6.80 p < 0.001; Z = 0.114 p = 0.99). e Heatmap representation of the time spent in EPM compartments in CTL, AD, and A mice. f Time in EPM open arms (Kruskal–Wallis test, H2/91 = 22.36; Z = 4.585 p < 0.001; Z = 3.432 p = 0.002; Z = 0.8381 p = 0.99) and g EPM open arm entries in AD and A mice compared to control mice (ANOVA, F(2, 91) = 5.258 p = 0.007; t = 2.763 p = 0.01, t = 2.912 p = 0.09; t = 0.403 p = 0.69; n = 28 CTL, n = 39 AD and n = 27 A mice, examined over 3 independent replicated experiments, bars represent mean ± s.e.m.). h Pearson correlation analyses of the time in open arms with the social interaction behaviors of socially stressed mice (n = 66, p = 0.74). i Heatmap representation of the time spent in the open field arena in CTL, AD, and A mice. j Time (%) in open field center (Kruskal–Wallis test, H2/52 = 17.55, p = 0.0001; Z = 2.728 p = 0.02; Z = 4.168 p = 0.0001; Z = 1.474 p = 0.42) and k number of open field center entries (ANOVA, F2/52 = 4.831 p = 0.01; t = 3.032 p = 0.01; t = 2.293 p = 0.05; t = 0.859 p = 0.39; n = 15 CTL, n = 19 AD and n = 21 A mice, bars represent mean ± s.e.m.). l Pearson correlation analyses of the time in open field center with the social interaction behaviors of socially stressed mice (n = 40, p = 0.017). In all panels, two-sided statistical analyses and post hoc tests were performed, *p < 0.05, **p < 0.01, ***p < 0.001, ns p > 0.05, for n number of C57BL6/J mice. See also Supplementary Figs. 1 and 2.
