MeCP2 S421A KI mice fail to show behavioral response to chronic imipramine treatment after chronic social defeat stress. a, Schematic representation of the chamber used for the social interaction test with dimensions. The interaction zone is defined as the region directly surrounding the chamber that is either empty (first 2.5 min of test) or contains a CD1 mouse (last 2.5 min of test). Chamber, interaction zone, and corners dimensions shown in inches. b, c, After 10 consecutive days of social defeat, KI and WT mice were tested for social interaction. The total time spent in the interaction zone (b) and the total time spent in the corners (c) in the presence of a CD1 aggressor. d, e, After 10 d of social defeat, KI and WT mice were treated acutely or chronically with imipramine for 28 d. On the day after the last injection, the mice were tested once again for social interaction. The total time in the interaction zone (d) and the total time in the corners (e) in the presence of a CD1 aggressor. n = 10 (WT) or 10 (KI) control and 17 (WT) or 22 (KI) defeated mice per group for b and c, and n = 8–13 mice per group for d and e. For b and c, *p < 0.001 defeated compared with control. For d and e, *p < 0.001 compared with control within each genotype, and #p < 0.001 WT chronic compared with WT acute.