Revisiting the validity of the mouse forced swim test: Systematic review and meta-analysis of the effects of prototypic antidepressants

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HighlightsSystematic reviews can help to evaluate external validity of models.We performed a meta-analysis on effects of prototypic antidepressants in the FST.As expected, the FST qualitatively detects antidepressant action.Results show significant heterogeneity of effect sizes for most drugs.We found limited dose-effect size relationship across laboratories laboratories.The validity of the test to compare efficacy across conditions is not clear.Within experiment D/R curves may help predict hierarchical relationship of interventions.One problem area regarding animal models for affective disorders is unclear reproducibility, including external validity or generalizability. One way to evaluate external validity is with systematic reviews and meta-analyses. The current study presents a meta-analysis of the effects of prototypic antidepressants in the mouse forced swim test (FST).We identified studies that examined effects of antidepressants in the FST in mice and used standard protocol, male mice and acute drug administration. We calculated Effect sizes using Cohen’s d, homogeneity using Q statistic and correlations using Pearson’s correlation.Results indicate that all drugs reduce immobility in the FST. However, effect sizes for most drugs are heterogeneous and do not show a consistent dose/response relationship across variability factors. Reducing variability by examining only one strain or data from individual laboratories partially increases dose response relationship.These findings suggest that whereas the FST is a valid tool to qualitatively screen antidepressant effects its validity in the context of hierarchical comparison between doses or compounds might be relevant only to single experiments.

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