Differential effect of chronic mild stress on anxiety and depressive-like behaviors in three strains of male and female laboratory mice.

Major depressive disorder is the most common psychiatric disorder worldwide. To understand mechanisms and search for new approaches to treating depression, animal models are crucial. Chronic mild stress (CMS) is the most used animal model of depression. Although CMS is considered a robust model of depression, conflicting results have been reported for emotion-related behaviors, which the intrinsic characteristics of each rodent strain could explain. To further shed light on the impact of genetic background on the relevant parameters commonly addressed in depression, we examined the effect of 4-weeks CMS on anxiety and depression-related behaviors and body weight gain in three strain mice (BALB/c, C57BL/6, and CD1) of both sexes. CMS reduced body weight gain in C57BL/6NCrl and CD1 male mice. C57BL/6 animals exhibited a more pronounced anxious-like behavior than CD1 and BALB/c mice in the light-dark box (LDB) and the elevated plus maze (EPM) tests, whereas BALB/c animals exhibited the more robust depressive-like phenotype in the splash test (ST), tail suspension test (TST) and forced-swimming test (FST). Under CMS, exposure did not affect anxiety-related behaviors in any strain but induced depression-like behaviors strain-dependently. CMS C57BL/6 and CD1 mice of both sexes showed depression-like behaviors, and CMS BALB/c male mice exhibited reduced depressive behaviors in the FST. These results suggest a differential effect of stress, with the C57BL/6 strain being more vulnerable to stress than the CD1 and BALB/c strain mice. Furthermore, our findings emphasize the need for researchers to consider mouse strains and behavioral tests in their CMS experimental designs.

Limited bedding nesting paradigm alters maternal behavior and pup's early developmental milestones but did not induce anxiety- or depressive-like behavior in two different inbred mice.

Animal models are crucial to understanding the mechanisms underlying the deleterious consequences of early-life stress. Here, we aimed to examine the effect of the limited bedding nesting (LBN) paradigm on early life development milestones and anxiety- and/or depression-like behavior in adolescent and adult mice from two inbred mice of both sexes. C57BL/6NCrl and BALB/c litters were exposed to the LBN paradigm postnatal day (PND) 2-9. Maternal behavior recording occurred on PND 3-9, and pups were weighed daily and examined to verify the eye-opening on PND 10-22. The male and female offspring underwent evaluation in the open field test, elevated plus-maze, and the forced swimming test during adolescence (PND 45-49) and adulthood (PND 75-79). We found that LBN impaired the maternal behavior patterns of both strain dams, mainly on C57BL/6NCrl strain. Also, LBN delayed the pup's eye-opening time and reduced body weight gain, impacting C57BL/6NCrl pups more. We also found that LBN decreased anxiety-related indices in adolescent and adult male but not female mice of both strains. Furthermore, LBN decreased depression-related indices only adolescent female and male BALB/c and female but not male C57BL/6NCrl mice. These findings reinforce the evidence that the LBN paradigm impairs the maternal behavior pattern and pup's early developmental milestones but does not induce anxiety- or depressive-like behavior outcomes during later life.