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. 2021 Nov 30;47(5):987–999. doi: 10.1038/s41386-021-01219-8

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Timeline for CORT treatment experiment. b–d Light–dark box test reveals increased anxiety-like behavior in mice treated with CORT. (2-way ANOVA, % Time in Light: genotype: F (1, 36) = 10.36, p < 0.01; Latency to Light: treatment: F (1, 36) = 11.47, p < 0.01). e–g Splash test reveals increased anxiety-like behavior in BDNF het-Met mice treated with CORT (2-way ANOVA, grooming latency: treatment × genotype: F (1, 36) = 6.523, p < 0.05; # of grooming sessions: treatment: F(1, 36) = 4.39, p < 0.05). h Complementary variables of behavior for both WT and BDNF het-Met were compiled to calculate a z-score, which show that CORT-treated mice displayed higher emotionality scores compared to vehicle-treated mice regardless of genotype (2-way ANOVA, treatment: F (1, 36) = 16.44, p < 0.001). i Timeline for CSDS treatment experiment. j, k The social interaction test reveals decreased anxiety-like behavior in RES mice. (2-way ANOVA, Time in SI Zone: interaction (susceptibility-by-housing) effect: F (1, 150) = 7.068, p < 0.01; SI Ratio: susceptibility effect: F (1, 150) = 243.2, p < 0.001). l Pie-chart depicting the proportion of mice raised in SH or EE and ranked RES or SUS after CSDS. The proportion of RES mice raised in EE (21%) was higher than the one of RES mice raised in SH (9%) (p < 0.05). Columns represent the mean ± S.E.M. of ten animals per group for the CORT model (a–h) and mean ± S.E.M. of 59 animals for SUS and 14 for RES in SH, as well as 49 animals for SUS and 32 for RES in EE (j, k). ^*/#p < 0.05; **p < 0.01; ^***/##p < 0.001. PND post-natal day, WT wild-type, BDNF het-Met heterozygous BDNF Val66Met, VEH vehicle, CORT corticosterone, CSDS chronic social defeat stress, SI social interaction, RES resilient, SUS susceptible, SH standard housing, and EE enriched environment.