Individual variability in female and male mice in a test-retest protocol of the forced swim test

Background: The challenges to embody the complexity of symptoms and biological mechanism of affective disorders question the value of animal models as well as their reproducibility and validity. Validity is further hindered by large individual variability in many models. Whereas individual variability presents a challenge, it can also be used to study susceptibility and resistance. One of the frequently used models for screening antidepressants and interventions related to depression is the forced swim test (FST). The FST is typically performed only once. Methods: The current study was designed with a number of objectives: (1) Examine the group effects of repeated FST (2) Examine the interaction between sex and repeated FST and (3) examine the consistency of individual variability across test and retest in the FST. We exposed ICR female and male mice to the FST 3 or 5 times with two days between exposures. Immobility time was analyzed across exposures at the group and the individual levels using repeated measures ANOVA as well as Pearson's correlations. Results: As expected, repeated exposure to the FST resulted in increased immobility across exposures with no consistent effect of sex. At the level of individual mice, immobility time showed correlation across exposures. Discussion: The current study demonstrates the effects of repeating the FST in both sexes with attention to individual variability. The results suggest that the FST can be used more than once and that mice show a consistent individual pattern of responding in the test.