Male SSTCre:γ2f/fmice are resilient to chronic stress-induced emotional behavior. A) Experimental design. B) Male SSTCre:γ2f/f mice were resilient to UCMS-induced reductions in weight gain as evidenced by a stress × genotype interaction (F1,385 = 11.23, p < 0.001, 3-way repeated measurement ANOVA). C,D) In the OFT, there was an interaction of stress x genotype in the total distance traveled (C) (F1,55 = 5.969, p = 0.018). UCMS increased locomotion of SSTCre:γ2f/f (p < 0.001, n = 14–15) and UCMS-exposed SSTCre:γ2f/f showed greater locomotion than UCMS-exposed γ2f/f controls (p = 0.015, n = 14–15). The center duration (D) was unaffected by stress and genotype. E) In the EPM, there was an anxiolytic-like genotype effect on % time spent on open arms (F1,40 = 17.04, p < 0.001), but no stress effect (F1,40 = 0.14, p = 0.71). Post hoc tests confirmed the anxiolytic phenotype of NS SSTCre:γ2f/f mice vs. NS γ2f/f controls (p = 0.046, n = 8–11) and UCMS SSTCre:γ2f/f mice vs. UCMS γ2f/f controls (p = 0.016, n = 9–15). F) In the NSFT, there was a stress effect on latency to feed (F1,53 = 14.44, p < 0.001) and a trend for a stress × genotype interaction (F1,53 = 2.841, p = 0.098). UCMS increased the latency to feed of γ2f/f mice (p = 0.0012, n = 15) but not SSTCre:γ2f/f mice (p = 0.47, n = 13–14). G) In the SSPT, there was an overall stress effect (F1,53 = 22.09, p < 0.001). UCMS reduced the grooming duration of γ2f/f (p < 0.001, n = 14–15) but not SSTCre:γ2f/f mice (p = 0.14, n = 13–15). H) The SPT showed a genotype effect, with a greater sucrose preference in SSTCre:γ2f/f compared to γ2f/f mice (F1,22 = 4.76, p = 0.04). However, post hoc comparisons of NS γ2f/f vs. NS SSTCre:γ2f/f (p = 0.45), and UCMS γ2f/f vs. UCMS SSTCre:γ2f/f (p = 0.41, n = 5–10) were not significant, and there was no UCMS effect (F1,22 = 0.78, p = 0.39), nor a UCMS X genotype interaction (F1,22 = 0.0042, p = 0.95). Data were analyzed by 2-way ANOVA and Tukey test. Bar graphs represent means ± SE. *p < 0.05, **p < 0.01, ***p < 0.001.