Mapping the evolution of the forced swim test across interpretation, welfare and pharmacology.

Abstract

The Porsolt Forced Swim Test (FST), primarily utilized for phenotyping and screening novel antidepressants in rodents, is one of the most widely used tests in depression research. Despite its popularity, this test has received increasing criticism mainly due to welfare concerns and interpretation discrepancies, a conflict that potentially reduces the predictive validity of this test through false positive results. To ensure both animal welfare and the reliable interpretation of reproducible test results, experiments must be designed and analyzed with utmost rigor to ensure the test is used appropriately. To assist with this, we provide a comprehensive, accessible database of all experimental setups and tested drugs in rats, to help avoid duplication of experiments and support future study design with adequate protocols that maximize animal welfare without compromising the research focus. While many reviews have covered the FST, none is as comprehensive as our systematic mapping review, which covers the 3907 manuscripts published on the FST in rats from 1977 until Dec 31, 2021. As the field remains divided over whether the FST portrays despair or rather adaptive coping and learning, we aim to inspire a consensus on the interpretation of the FST, thereby strengthening its translational validity and relevance as a potential component of a wider test battery for depression. We intend to raise awareness for these critical aspects of the FST, to balance the current reliance on it and minimize animal distress until valid (non-animal) alternatives are developed, which also cover the behavioral dimension of depression.