Time to end the forced swim test

Recent publications questioning the continued reliance on a contentious animal research test known as the ‘Forced Swim Test’ has brought the issue to the attention of the UK Government. The Government has asked the Animals in Science Committee to review the evidence and provide feedback on use of the test by the end of January 2023.

FRAME refute the Forced Swim Test as a model of human depression and advocate for more time and funding to develop non-animal replacements for the test in drug development and testing.

What is the Forced Swim Test

The Forced Swim Test became popular in 1977 when Roger D. Porsolt used it as a ‘behavioural despair test’ for the assessment of antidepressant drugs. The test has garnered strong criticism for many years over animal welfare concerns and is once again in the spotlight after more evidence questioning the scientific value of the test, particularly in light of available alternatives today.

In the Forced Swim Test rats or mice are placed in a container of water, with straight sides and no way of escape or place to rest, so they are forced to swim. The measurements taken look at the time the rodent spends moving in the water, and how much time they remain stationary (floating). It has been reported that initially scientists believed that when the mouse or rat stopped swimming this was a sign of the animal ‘giving up’ and therefore could, and has, been used as a model of depression for research into the human condition. The use of this test as a model of depression remains, unsurprisingly, unproven. This is one of the factors driving the recent Government call for a review of the test. Whilst there is no doubt that the Forced Swim Test cannot, and should not, be used as an animal model for depression research, many in the scientific community still believe in is an essential tool for assessing the efficacy of potential antidepressant treatments(1). To the point that the test is often thought of as a regulatory requirement in the development of antidepressant drugs. Whilst this is not the case, and the FST may have a role in the screening of anti-depressant drugs, it should not be considered or used in research today as a model of depression in people.

Animals in Science Committee commissioned to provide policy advice on the Forced Swim Test

A paper published in October 2021 in the journal Regulatory Toxicology and Pharmacology(2) clarified that the forced swim test is not a regulatory requirement for the development of new antidepressants and recommended that alternative approaches be used instead. The paper was co-authored by staff from the NC3Rs and the UK Medicines and Healthcare products Regulatory Agency.

In August 2022, the UK Government decided that a review of the use of the Forced Swim Test was warranted and commissioned the Animals in Science Committee, an advisory, non-departmental public body, to review the evidence of alternative methods and appropriate justification for use of the test under the Animals in Scientific Procedures Act 1986 (3). The review must give due consideration to the legitimate requirements of science and industry and to the protection of animals. The specific question posed to the Animals in Science Committee is ‘How should the 3Rs be applied regarding the forced swim test, drawing on the available evidence and licence review?’

On the 14th October 2022, Professor David Main, Chair of the Animals in Science Committee, published a letter accepting the commission(4). The committee will consider evidence from a review of licenses that include or make reference to the Forced Swim Test. As part of their evidence gathering they are also looking to engage with stakeholder organisations, in particular those that can provide scientific, peer-reviewed evidence on use of the test, and/or alternative methods. Evidence can be shared through submission of a questionnaire by the 11th of November 2022.

FRAME View

At FRAME we believe the use of the Forced Swim Test as a model of depression should be ended, and more energy, time and funding put into the development of alternative, non-animal screening tools for antidepressants.

Concerns around continued use of this test has sparked recent conversations and calls for change at government level not just in the UK but across the globe. The most recently in Australia(5).

There are no scientific reasons evidencing the test as a model of depression in people, and it is not a mandatory requirement for the development of any drug. Considering the mounting evidence highlighting the poor translational value of this model and the undeniable stress caused to the animals used, it would be unethical to continue using, or licensing projects that use the Forced Swim Test for this, or likely any other purpose.

Juliet Dukes, Research Manager at FRAME explains ‘Continued use of the Forced Swim Test has been a scientific and ethical concern for some time. It does not reflect the complexity of mental health issues in people and is highly stressful for the animals. Undoubtedly future research should be focussing on the development of human relevant biomarkers and cell-based systems which can be used to evaluate depression and responses to potential treatments. We believe there is no reason for this test to be used in research. We will be submitting evidence to the Animals in Science Committee review and actively encourage those from the scientific community with relevant evidence for alternative approaches for assessing depression or anti-depressant drug activity to do the same.’