The forced swim test is widely discredited – it has been shunned by leading scientists and universities. Show your support for ending the use of the test by adding your name to the open letter, below. Please note that it may be shared with policymakers, decision-makers, and relevant media outlets.
Fill out the form below to add your name to the list of signatories of this open letter. If you have any questions or would like a copy of this letter to send on your own, please e-mail [email protected].
Open Letter
The forced swim test is not a valid or reliable scientific method, and its use must be ended. The forced swim test (FST), or Porsolt test, is a behavioural experiment initially developed for screening antidepressant drugs1 and which was later adopted in an attempt to model depression.2 It involves placing a small animal in a beaker filled with water that does not have an escape platform and recording the latency to stop swimming and the duration of floating.3,4 Historically, this observation has been interpreted as “behavioural despair”5 under the assumption that animals with depression-like behaviour “give up swimming earlier than those [who] are not depressed” and that antidepressant drugs reverse this effect.6
Its use in depression and anxiety research has been heavily criticised for various reasons. For example, rather than behavioural despair, floating in the FST may be indicative of learning, a way to conserve energy, or adaptation to a new environment.7-9 This has resulted in many institutional bodies advising against the use of the FST for modelling depression and/or anxiety.10-15 Additionally, its use as a screening tool is also under question, given that it cannot reliably predict the efficacy of antidepressant drugs.16–26 As a result, numerous pharmaceutical companies and universities have declared that they do not intend to use the FST in the future.27
The FST has also been discouraged on the grounds of animal welfare – the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research identifies the FST as “highly contentious” and “under considerable scrutiny” due to “its severity and effect on animal welfare”.28 Rodents often defecate during the procedure, which is thought to be a fear response,29 and there is a documented risk of accidental drowning or water aspiration.30 The test is considered acutely stressful for animals, which has resulted in it also being adopted to model post-traumatic stress disorder.31 However, there are concerns about its validity for this purpose, too. Because of the neurobiological differences between humans and other animals, it is doubtful that the behaviour animals display when subjected to this experiment can be relevant to the human clinical condition.32-36
Despite the scientific and welfare concerns, the test is still widely used, and many of those who fund, authorise, or use the FST appear not to be aware of the debate around its use and interpretation.
We, the undersigned, call for an end to the use of the FST. The FST should not pass a harm-benefit analysis and, consequently, there should be no further authorisation of the test in cases where it is known to be unfit for purpose. As well as causing harm to animals, continuing to authorise use of the FST undermines the integrity of scientific output and public confidence in the rigour with which scientific procedures on animals are evaluated and authorised.
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Deutsche Übersetzung
Der Forced Swim Test ist keine valide oder zuverlässige wissenschaftliche Methode und sollte nicht mehr angewendet werden. Der Forced Swim Test (FST), auch Porsolt-Test genannt, ist ein Verhaltensexperiment, das ursprünglich zur Untersuchung von Antidepressiva entwickelt1 und später zur Modellierung von Depressionen eingesetzt wurde.2 Dabei wird ein kleines Tier in einen mit Wasser gefüllten Behälter ohne Fluchtmöglichkeit gesetzt und die Latenzzeit bis zum Aufhören des Schwimmens sowie die Dauer des Treibenlassens aufgezeichnet.3,4 In der Vergangenheit wurde diese Beobachtung als „Verzweiflungsverhalten” interpretiert,5 unter der Annahme, dass Tiere mit depressionsähnlichem Verhalten „früher aufhören zu schwimmen als nicht depressive Tiere” und dass Antidepressiva diesen Effekt umkehren.6
Die Verwendung in der Depressions- und Angstforschung wurde aus verschiedenen Gründen heftig kritisiert. Beispielsweise könnte das Treibenlassen im FST eher ein erlerntes Verhalten, eine Möglichkeit zur Energieeinsparung oder eine Anpassung an eine neue Umgebung sein als Verzweiflung.7–9 Dies hat dazu geführt, dass zahlreiche institutionelle Gremien von der Verwendung des FST zur Modellierung von Depressionen und/oder Angstzuständen abraten. 10–15 Darüber hinaus wird auch seine Verwendung als Screening-Instrument in Frage gestellt, da der Test die Wirksamkeit von Antidepressiva nicht zuverlässig vorhersagen kann.16–26 Infolgedessen haben zahlreiche Pharmaunternehmen und Universitäten erklärt, dass sie den FST in Zukunft nicht mehr durchführen wollen.27
Der FST wird auch aus Tierschutzgründen abgelehnt – das britische National Centre for the Replacement, Refinement and Reduction of Animals in Research (Nationales Zentrum für die Ersetzung, Verfeinerung und Reduzierung von Tieren in der Forschung) stuft den FST aufgrund „seiner Schwere und seiner Auswirkungen auf das Wohlergehen der Tiere” als „höchst umstritten” und „unter genauer Beobachtung” ein.28 Nagetiere entleeren während des Verfahrens häufig ihren Darm, was als Angstreaktion gedeutet wird,29 und es besteht ein dokumentiertes Risiko des versehentlichen Ertrinkens oder der Wasseraspiration.30 Der Test gilt als akut stressig für Tiere, weshalb er auch zur Modellierung posttraumatischer Belastungsstörungen eingesetzt wird.31 Allerdings gibt es auch Bedenken hinsichtlich seiner Eignung für diesen Zweck. Aufgrund der neurobiologischen Unterschiede zwischen Menschen und anderen Tieren ist es zweifelhaft, dass das Verhalten, das Tiere bei diesem Versuch zeigen, für den klinischen Zustand des Menschen relevant ist.32–36
Trotz der wissenschaftlichen und tierschutzrechtlichen Bedenken wird der Test nach wie vor häufig angewendet. Viele derjenigen, die den FST finanzieren, genehmigen oder anwenden, scheinen sich der Debatte über seine Verwendung und Interpretation nicht bewusst zu sein.
Wir, die Unterzeichnenden, fordern die Einstellung des FST. Der FST dürfte eine Kosten-Nutzen-Analyse nicht bestehen und daher in Fällen, in denen er bekanntermaßen für den vorgesehenen Zweck ungeeignet ist, nicht weiter zugelassen werden. Eine zukünftige Zulassung des FST schadet nicht nur den Tieren, sondern untergräbt auch die Integrität wissenschaftlicher Ergebnisse und das Vertrauen der Öffentlichkeit in die Strenge, mit der wissenschaftliche Verfahren an Tieren bewertet und zugelassen werden.
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References
1 Porsolt RD, Anton G, Blavet N, et al. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978;47(4):379-391. doi:10.1016/0014-2999(78)90118-8
2 Molendijk ML, de Kloet ER. Forced swim stressor: trends in usage and mechanistic consideration. Eur J Neurosci. 2022;55(9-10):2813-2831. doi:10.1111/ejn.15139
3 Castagné V, Porsolt RD, Moser P. Use of latency to immobility improves detection of antidepressant-like activity in the behavioral despair test in the mouse. Eur J Pharmacol. 2009;616(1-3):128-133. doi:10.1016/j.ejphar.2009.06.018
4 Lucki I. Behavioral despair. In: Stolerman IP, ed. Encyclopedia of Psychopharmacology. Springer;2010:202-204. Accessed 15 August 2025. doi.org/10.1007/978-3-540-68706-1_141
5 Yankelevitch-Yahav R, Franko M, Huly A, et al. The forced swim test as a model of depressive-like behavior. J Vis Exp. 2015;97:e52587. doi:10.3791/52587
6 Kraeuter AK, Guest PC, Sarnyai Z. The forced swim test for depression-like behavior in rodents. In: Guest P, ed, Pre-Clinical Models. Methods in Molecular Biology, vol 1916. Humana Press;2019:75-80. doi:10.1007/978-1-4939-8994-2_5
7 Molendijk ML, de Kloet ER. Immobility in the forced swim test is adaptive and does not reflect depression. Psychoneuroendocrinology. 2015;62:389-391. doi:10.1016/j.psyneuen.2015.08.028
8 Molendijk ML, de Kloet ER. Coping with the forced swim stressor: current state-of-the-art. Behav Brain Res. 2019;364:1-10. doi:10.1016/j.bbr.2019.02.005
9 Commons KG, Cholanians AB, Babb JA, et al. The rodent forced swim test measures stress-coping strategy, not depression-like behavior. ACS Chem Neurosci. 2017;8(5):955-960. doi:10.1021/acschemneuro.7b00042
10 Animals in Science Committee. Research and analysis: advice on the use of the forced swim test. Animals in Science Committee response to a ministerial commission for advice. July 2023. Accessed 15 August 2025. https://www.gov.uk/government/publications/advice-on-the-use-of-the-forced-swim-test/advice-on-use-of-the-forced-swim-test-accessible.
11 Sewell F, Waterson I, Jones D, et al. Preclinical screening for antidepressant activity – shifting focus away from the forced swim test to the use of translational biomarkers. Regul Toxicol Pharmacol. 2021;125:105002. doi:10.1016/j.yrtph.2021.105002
12 British Association for Psychopharmacology, Laboratory Animal Science Association, The Physiological Society, and Understanding Animal Research. Factsheet on the forced swim test. 2020. Accessed 15 August 2025. https://www.lasa.co.uk/wp-content/uploads/2020/10/Forced-Swim-Test-Factsheet-final-002.pdf
13 Use of primates and other animals in medical research in New South Wales. New South Wales Parliament, Legislative Council, Portfolio Committee No.2, Health; 2022. Accessed 15 August 2025. https://www.parliament.nsw.gov.au/lcdocs/inquiries/2857/Report%20No.%2059%20-%20PC%202%20-%20Use%20of%20primates%20and%20other%20animals%20in%20medical%20research%20in%20New%20South%20Wales.pdf
14 Parliament of New South Wales. New South Wales Government Response: Inquiry into the use of primates and other animals in medical research in New South Wales. January 2023. Accessed 15 August 2025. https://www.parliament.nsw.gov.au/lcdocs/inquiries/2857/Government%20Response%20-%20Report%20No.%2059%20-%20PC%202%20-%20Use%20of%20primates%20and%20other%20animals%20in%20medical%20research%20in%20New%20South%20Wales.pdf
15 New Zealand Parliament, Economic Development, Science and Innovation Committee. Petition: end the use of the forced swim test in New Zealand. 2020. Accessed 15 August 2025. https://www.parliament.nz/resource/en-NZ/SCR_95117/50c60dcb87e9ee8360c19c45739ff919854c66c8
16 National Animal Ethics Advisory Committee. Comment on the Porsolt forced swim test. Reviewed November 2021. Accessed 15 August 2025. https://www.naeac.org.nz/assets/NAEAC-documents/Comment-on-the-Porsolt-forced-swim-test.pdf
17 Bogdanova OV, Kanekar S, D’Anci KE, et al. Factors influencing behavior in the forced swim test. Physio Behav. 2023;13(118):227-239. doi:10.1016/j.physbeh.2013.05.012
18 Commons KG, Cholanians AB, Babb JA, et al. The rodent forced swim test measures stress-coping strategy, not depression-like behavior. ACS Chem Neurosci. 2017;8(5):955-960. doi:10.1021/acschemneuro.7b00042
19 Hodge RD, Bakken TE, Miller JA, et al. Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019;573(7772):61-68. doi:10.1038/s41586-019-1506-7
20 Jennings EM, Okine BN, Olango WM, et al. Repeated forced swim stress differentially affects formalin-evoked nociceptive behaviour and the endocannabinoid system in stress normo-responsive and stress hyper-responsive rat strains. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:181-189. doi:10.1016/j.pnpbp.2015.05.008
21 Kara NZ, Stukalin Y, Einat H. Revisiting the validity of the mouse forced swim test: systematic review and meta-analysis of the effects of prototypic antidepressants. Neurosci Biobehav Rev. 2018;84:1-11. doi:10.1016/j.neubiorev.2017.11.003
22 Kokras N, Antoniou K, Mikail HG, et al. Forced swim test: what about females? Neuropharmacology. 2015;99:408-421. doi:10.1016/j.neuropharm.2015.03.016
23 Kraeuter AK, Guest PC, Sarnyai Z. The forced swim test for depression-like behavior in rodents. In: Guest P, ed. Pre-Clinical Models. Methods in Molecular Biology, vol 1916. Humana Press;2019:75-80. doi:10.1007/978-1-4939-8994-2_5
24 Mul JD, Zheng J, Goodyear LJ. Validity assessment of 5 day repeated forced-swim stress to model human depression in young-adult C57BL/6J and BALB/cJ mice. eNeuro. 2016;3(6)ENEURO.0201-16.2016. doi:10.1523/ENEURO.0201-16.2016
25 Manolova AO, Stepanichev MY, Gulyaeva NV, et al. Behavior of rats in a forced swimming test is not an unambiguous predictor for the development of anhedonia in chronic stress. Neurosci Behav Physi. 2019;49:1016-1021. doi:10.1007/s11055-019-00831-y
26 Possamai F, dos Santos J, Walber T, et al. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test. Prog Neuropsychopharmacol Biol Psychiatry. 2015;58:15-21. doi:10.1016/j.pnpbp.2014.10.017
27 Suman PR, Zerbinatti N, Theindl LC, et al. Failure to detect the action of antidepressants in the forced swim test in Swiss mice. Acta Neuropsychiatr. 2018;30(3):158-167. doi:10.1017/neu.2017.33
28 Trunnell ER, Carvalho C. The forced swim test has poor accuracy for identifying novel antidepressants. Drug Discov Today. 2021; 26(12):2898-2904. doi:10.1016/j.drudis.2021.08.003
29 People for the Ethical Treatment of Animals. Victories! PETA is ending near-drowning experiments on animals. PETA.org. Updated 2023. Accessed 15 August 2025. https://www.peta.org/features/peta-ends-near-drowning-tests-small-animals
30 National Centre for the Replacement, Refinement and Reduction of Animals in Research. The forced swim test is not a regulatory requirement for the development of new antidepressants. July 2021. Accessed 15 August 2025. https://nc3rs.org.uk/news/forced-swim-test-not-regulatory-requirement-development-new-antidepressants
31 Sutherland RJ, McDonald RJ. Hippocampus, amygdala, and memory deficits in rats. Behav Brain Res. 1990;37(1):57-79. doi:10.1016/0166-4328(90)90072-m
32 Use of primates and other animals in medical research in New South Wales. New South Wales Parliament, Legislative Council, Portfolio Committee No.2, Health; 2022. Accessed 15 August 2025. https://www.parliament.nsw.gov.au/lcdocs/inquiries/2857/Report%20No.%2059%20-%20PC%202%20-%20Use%20of%20primates%20and%20other%20animals%20in%20medical%20research%20in%20New%20South%20Wales.pdf
33 Barroca NCB, Della Santa G, Suchecki D, et al. Challenges in the use of animal models and perspectives for a translational view of stress and psychopathologies. Neurosci Biobehav Rev. 2022;104(104771). doi:10.1016/j.neubiorev.2022.104771
34 National Centre for the Replacement, Reduction and Refinement of Animals in Research. The forced swim test is not a regulatory requirement for the development of new antidepressants. July 2021. Accessed 15 August 2025. https://nc3rs.org.uk/news/forced-swim-test-not-regulatory-requirement-development-new-antidepressants
35 People for the Ethical Treatment of Animals Foundation. The Research Modernisation Deal. Updated December 2022. Accessed 15 August 2025. https://www.peta.org.uk/wp-content/uploads/2020/05/PETA-Research-Modernisation-Deal-UK-EU-V1.3.pdf
36 Garner JP. The significance of meaning: why do over 90% of behavioral neuroscience results fail to translate to humans, and what can we do to fix it? ILAR J. 2014;55(3):438-456. doi:10.1093/ilar/ilu047
