(A) GPR158 protein levels are increased in the mPFC of mice chronically treated with corticosterone (n = 9–10 mice/group, Student’s t test). Top panel depicts corticosterone paradigm. Mice treated with corticosterone exhibited a significant correlation between GPR158 protein levels and immobility in the TST (Pearson R2 = 0.4605, p=0.0014). (B) Mice injected acutely with corticosteroid (Acute Cort., 20 mg/kg) show no difference in GPR158 levels compared to vehicle (Veh) treatment (n = 5, Student’s t test; ns, not significant). (C) Western blot quantification of GPR158 in primary cortical neurons cultured for 21 days in vitro and treated with 0.5 µM dexamethasone (Dex) from DIV 14 to DIV21 (n = 3, Student’s t test, *p<0.05). (D) GPR158 protein levels in the mPFC of mice subjected to physical restraint stress and treated with RU-486. To induce chronic stress mice underwent a 17 day PRS period. On the last three days of the stress paradigm, mice were injected with RU-486 (10 mg/kg) or vehicle prior to being subjected to PRS. The mPFC was isolated 30 min following last episode of PRS (day 17). Stressed mice treated with RU-486 have a decrease in GPR158 protein levels compared to saline treatment (n = 4–5 mice/group, Two-way ANOVA with Tukey post hoc test, **p<0.01, ***p<0.001). Data shown as means ± SEM (Veh, vehicle; Ctrl, control; PRS, physical restraint stress; Cort., corticosterone).