Strain-dependent sex differences in a long-term forced swim paradigm

Area of Science:

• Neuroscience
• Behavioral Science
• Animal Models

Background:

• Women experience trauma- and stressor-related disorders at twice the rate of men.
• Understanding the neural and behavioral stress response in females is crucial for developing better therapies.
• The forced swim test (FST) is a key animal model for studying stress coping mechanisms.

Purpose of the Study:

• To investigate how sex, rat strain (Sprague Dawley and Long Evans), and housing affect active and passive coping strategies in a modified, long-term FST.
• To explore the dissociation between innate and learned coping responses across two FST sessions.
• To examine the role of the medial prefrontal cortex (mPFC) in sex differences in FST behavior.

Main Methods:

• Utilized a modified 4-week forced swim test (FST) paradigm in Sprague Dawley (SD) and Long Evans (LE) rats.
• Conducted immunohistological analysis to assess neural activity, specifically c-fos expression.
• Analyzed behavioral responses including immobility, climbing, and headshakes across two FST sessions.

Main Results:

• Significant strain × sex interactions were observed for both passive (immobility) and active (climbing, headshakes) responses.
• SD rats showed stable sex differences in immobility, while LE rats did not.
• Males, unlike females, demonstrated a cross-test increase in immobility, indicating different learning processes. Sex differences in behavior correlated with c-fos expression in the mPFC.

Conclusions:

• Sex and strain significantly influence coping strategies in the FST, with distinct patterns observed between male and female rats.
• The medial prefrontal cortex (mPFC) may play a role in the sexually dimorphic behavioral responses observed in the FST.
• These findings highlight the importance of considering sex and strain in animal models of stress and developing sex-specific therapeutic interventions.