A proposal for refining the forced swim test in Swiss mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• The forced swim test (FST) is widely used for antidepressant screening in rodents.
• However, the FST is also sensitive to motor stimulants, potentially confounding results.
• Standardized behavioral scoring is needed to improve FST specificity.

Purpose of the Study:

• To standardize and validate a method for registering active and passive behaviors in Swiss mice during the FST.
• To enhance the specificity of the FST for antidepressant screening by differentiating from motor stimulants.

Main Methods:

• Adult male Swiss mice underwent the 6-minute FST without treatment or after administration of saline, antidepressants (imipramine, desipramine, fluoxetine), or stimulants (caffeine, apomorphine).
• Behavioral parameters (immobility, swimming, climbing latency, frequency, duration) were scored in 6, 4, 2, or 1-minute bins.
• Principal Components Analysis was used to analyze behavioral data.

Main Results:

• Antidepressants and stimulants similarly affected parameters grouped into principal components.
• Stimulant effects on climbing were better distinguished from antidepressants when analyzed during the last 4 minutes of the FST.
• Antidepressant effects on immobility were better distinguished from saline when parameters were scored in the first 2 minutes.

Conclusions:

• The proposed method effectively distinguishes antidepressants from motor stimulants in the FST using Swiss mice.
• This refinement has the potential to reduce the number of animals required for preclinical antidepressant evaluation.