Fig. 1: Exposure to enriched environment shortens the time to antidepressant action of venlafaxine.

A Experimental timeline. Animals were exposed to corticosterone (CORT mice, n = 63) or vehicle (VEH mice, n = 12) in the drinking water during the whole experiment. Starting at week 0, CORT mice received a treatment of venlafaxine or vehicle for 8 weeks either in their home cage (CORT-VLX mice, n = 12 and CORT-VEH mice, n = 12) or in an enriched environment (CORT-EE mice, n = 16 and CORT-EE-VLX mice, n = 23). Behavior was evaluated after 2 (B, C) and 8 (D, E) weeks of treatment. B, D Emotional and (C, E) cognitive tests were analyzed using two-way ANOVAs with housing condition and treatment as main factors. Emotional and cognitive z-scores were established based on VEH mice. After 2 weeks of treatment, a significant effect of housing condition (F_(1;59) = 27.0, p < 0.001) and housing condition × treatment interaction (F_(1;59) = 4.16, p < 0.05) were found for emotional z-score. A significant effect of housing condition was detected for cognitive z-score (F_(1;59) = 32.0, p < 0.001). After 8 weeks of treatment, ANOVA revealed a significant effect of housing condition, treatment and housing condition × treatment interaction for the emotional (F_(1;44) = 21.0, p < 0.001, F_(1;44) = 14.9, p < 0.001, and F_(1;44) = 5.57, p < 0.05, respectively) and the cognitive (F_(1;44) = 8.39, p < 0.01, F_(1;44) = 10.4, p < 0.01, and F_(1;44) = 19.5, p < 0.001, respectively) z-scores. The gray shaded area shows mean ± SEM values for VEH mice. In all other groups, data represent mean ± SEM and dots illustrate individual values. Post-hoc analysis when appropriate: **p < 0.01, ***p < 0.001 indicate significant differences compared to CORT-VEH group. ^$p < 0.05, ^$$$p < 0.001 indicate significant differences compared to CORT-VLX group.