REVIEW article
Front. Anim. Sci.
Sec. Animal Welfare and Policy
This article is part of the Research TopicBehavioral Assessment as an Indicator of Health and Welfare of Animals used for Food-Production or Research PurposesView all 6 articles
Re‐Evaluating the Forced Swim Test: Ethical, Scientific, and Regulatory Drivers for Validated Alternatives
Provisionally accepted
Parissa Barai1
Vaishnavi Pogakula1
Jagnoor Singh Sandhu1,2*Amrita Parida1
Krishnadas Nandakumar1
Gollapalle L Viswanatha1- 1Manipal Academy of Higher Education, Manipal, India
- 2Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
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The forced swim test (FST), a controversial rodent assay developed in the 1970s, measures immobility as "behavioral despair" to screen antidepressants. Despite its utility in identifying monoaminergic drugs, its validity is disputed: immobility may reflect adaptive energy conservation, not depression, whereas ethical concerns include distress, hypothermia, and hypoxia. Regulatory bodies (the UK to India) now restrict FST, citing poor human translatability. Global bans have spurred the adoption of alternatives (e.g., sucrose preference tests, and human iPSC-derived models). However, challenges persist in validation, cost, and regulatory acceptance. Case studies reveal postban innovation (e.g., UK universities shifting to AI-driven assays), whereas public advocacy intensifies demand for humane research. Emerging technologies, optogenetics, organ-on-a-chip systems, and biomarker-based AI analytics offer paths to human-relevant depression research without animal distress. This review critiques FST's scientific limitations, analyzes the ethical-policy shifts driving its phase-out, and evaluates alternatives. We argue for harmonized global standards to incentivize alternative validation, reformed ethical oversight, and collaborative frameworks bridging industry, academia, and regulators. The future of antidepressant screening lies in ethically aligned, human-centric models that transcend the constraints of the FST.
Keywords: Animal ethical regulations, Animal Welfare, Antidepressant screening alternatives, FST validity, Translational depression models
Received: 25 Aug 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Barai, Pogakula, Sandhu, Parida, Nandakumar and Viswanatha. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jagnoor Singh Sandhu
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