Housing conditions’ role in female depression models
lab animal
Research highlights
Depression
https://doi.org/10.1038/s41684-026-01733-6
Housing conditions’ role in female depression models
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Depression affects more than 280 million
people worldwide and remains a major
public health challenge due to its complex
pathophysiology. Epidemiological studies
consistently report a higher prevalence
of depression in women than in men,
pointing to sex-specific mechanisms
underlying disease vulnerability. In pre
clinical research, social defeat stress (SDS)
is among the most used paradigms for
modeling depression-like phenotypes
and shows strong construct, predictive
and face validity in male rodents. However,
using the SDS paradigm with female mice
remains difficult because males rarely
display spontaneous aggression toward
females. Vicarious social defeat stress (VDS)
is a potential non-physical alternative
that induces psychological stress through
witnessing social defeat rather than
direct confrontation.
A study in Experimental Animals analyzes whether restricting post-stress sensory
contact with male mice could improve the
reproducibility of behavioral outcomes in
a female VDS paradigm. Female mice were
exposed to daily VDS sessions using either
a conventional paradigm or to conditions
designed to limit sensory exposure to male
aggressors after stress. Following each
witnessing session, females were housed
either individually (single-housed; SH) or
together with another female (pair-housed;
PH) in a separate cage until the next exposure.
Researchers assessed social behavior using the
social interaction (SI) test, and also evaluated
physiological parameters and estrous cycle
stage. PH females showed social avoidance
when compared with SH and estrous cycle
stage did not modulate SI performance. In
contrast, housing conditions altered females’
physiology. Compared with PH mice, SH mice
showed reduced food intake, increased water
consumption and diminished body weight
gain, regardless of VDS exposure.
These results show that post-stress housing conditions influence physiological
outcomes and may confound interpretations of stress susceptibility in female mice.
Overall, these data can be used to refine the
female-appropriate VDS protocol and to
understand the role of housing condition in
psychological stress paradigms.
Jorge Ferreira
Original reference: Yajima Y., Takahashi A. & Toyoda A.
Exp. Anim. (2026) https://doi.org/10.1538/expanim.25-0112.
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