Rodent chronic variable stress procedures: A disjunction between stress entity and impact on behaviour.

Area of Science:

• Neuroscience
• Behavioral Science
• Animal Models of Depression

Background:

• Chronic variable stress (CVS) is a common method for modeling depression in rodents.
• The impact of study design on experimental outcomes in CVS models is not well understood.
• Existing hypotheses suggest longer or more complex CVS procedures should yield larger effect sizes.

Purpose of the Study:

• To systematically document study design characteristics of published rodent CVS procedures.
• To measure effect sizes in commonly used behavioral tests evaluating CVS effects.
• To investigate correlations between CVS procedure design and behavioral test effect sizes.

Main Methods:

• Systematic literature search of PubMed for rodent CVS studies.
• Documentation of CVS procedure duration, burden (number of stressors), and diversity (types of stressors).
• Calculation of effect sizes for the sucrose preference test (SPT), tail suspension test (TST), forced swim test (FST), open field test (OFT), and elevated plus maze (EPM).
• Statistical analysis using linear models and Pearson correlations to assess relationships.

Main Results:

• Most studies employed unique CVS procedures.
• Contrary to hypotheses, longer and more diverse CVS procedures were associated with smaller FST effect sizes.
• Positive correlations were observed between TST and FST effect sizes, and between OFT and EPM effect sizes.
• Strongest positive correlations were found between EPM and TST, and EPM and FST.

Conclusions:

• The design of CVS procedures has a complex and sometimes counterintuitive impact on behavioral test outcomes.
• Observed correlations between behavioral tests suggest potential shared underlying mechanisms, but also highlight inconsistencies.
• Findings question current understanding of CVS procedures and the interpretation of behavioral tests in depression modeling.