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Sex Differences in Behavioral Responses to Chronic Unpredictable Mild Stress in Swiss Mice
Rachel de Barros-Telles1, Ana Clara F da Silva1, Isabelle Medeiros1
1Laboratory of Molecular Pharmacology, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
The European Journal of Neuroscience
|July 16, 2026
Summary
Female mice exhibit heightened sensitivity to chronic stress, showing earlier and more pronounced behavioral changes than males. Swiss mice demonstrate resilience, requiring extended stress exposure to develop depressive-like symptoms.
Area of Science:
- Neuroscience
- Behavioral Science
- Endocrinology
Background:
- Sex differences in stress responses are recognized but temporal dynamics are unclear.
- Limited research compares sex differences in stress-induced behaviors using genetically diverse models.
- Understanding these differences is crucial for stress-related disorder research.
Purpose of the Study:
- To investigate the time course of sex-dependent behavioral responses to chronic unpredictable mild stress (CUMS).
- To compare male and female Swiss mice's behavioral and hormonal reactions to varying durations of CUMS.
- To assess the stress resilience of the Swiss mouse strain.
Main Methods:
- Adult male and female Swiss mice were subjected to 4, 6, or 8 weeks of CUMS.
- Behavioral assessments included open field (OF) exploration and forced swimming tests.
- Serum corticosterone levels were quantified.
Main Results:
- Females showed decreased OF center exploration at 4 weeks, with no changes at later time points.
- Males exhibited reduced OF center exploration at 4, 6, and 8 weeks.
- Extended CUMS (8 weeks) increased immobility in the forced swimming test, particularly in females.
- Only females displayed elevated corticosterone levels after 8 weeks of CUMS.
Conclusions:
- Females are more susceptible to stress-induced maladaptive behaviors than males, aligning with clinical observations.
- Swiss mice exhibit significant stress resilience, needing prolonged stress exposure for depressive-like behavioral changes.
- The study highlights the importance of considering sex and genetic variability in stress research.
