What the Forced Swim Test involves

The Forced Swim Test, also known as the Porsolt swim test or the behavioural despair test, is used in behavioural pharmacology and neuroscience to try and assess depressive-like behaviour in rodents, particularly mice and rats. It was developed by Roger D. Porsolt and colleagues in the late 1970s.^{1, 2}

A mouse or rat is placed in a container filled with water from which they cannot escape. The water is supposed to be deep enough that the animal cannot touch the bottom, and is unable to climb out of the container. The rodent is left to swim for a fixed period, typically around 5-6 minutes.

While mice are usually put through this procedure once, the protocol for rats involves “acclimating the rats to the test situation”. This means the rat is put through the Forced Swim Test prior to the real test, just to make them aware that this water cylinder is truly inescapable. The protocol calls for this pre-test to run 15min. All just to ensure that the rats give up early enough the second time around to “induce a stable, high level of immobility”.³

Why it’s used

In the 1960s and 1970s, there was a rising need for a screening tool for anti-depressants that didn’t rely on drug interactions. The Forced Swim Test was one of the earliest solutions. Researchers watch how long it takes for the animal to “give up” and how long they stay still. If the animals stop moving a lot, it's seen as a sign they might be feeling hopeless or down.³ This “behavioural despair” can also be seen in dogs being shocked with no escape⁴ or infant monkeys⁵ in solitary confinement.

Therefore, scientists took to this test to see if different drugs can make the animals act less "hopeless". This was a very misguided attempt to try and figure out if something could be used to treat depression or mood problems.

However, the evidence now shows that the animal's behaviour in the Forced Swim Test represents a survival strategy rather than a state of ‘depression.’

More recently, the Forced Swim Test is also used in experiments around stress and anxiety research, as a means to cause stress to the animals.⁶

Why it is cruel

The animals do not know that they will be taken out of the cylinder. For them it is a live or death situation. The whole principle rests upon causing despair.

But even apart from the obvious, this test is treating the animals poorly. The water temperature is supposed to be 25°C, which is much too cold for rodents and has been shown to cause them hypothermia.⁷

As the protocol does not state how to handle the animals afterwards, it is up to the researcher. If they just put them back into their cages, it takes a long time for them to regain their normal body temperature.⁸ The researcher can also take the time to dry and warm them up again, or (depending on the study design), the animals might be killed.⁹

Why it doesn’t work

The Forced Swim Test doesn’t predict how humans will respond to drugs and has no relevance to human depression.

The causes of depression are not adequately understood yet - many different factors could contribute to symptoms of depression in humans.¹⁰ Trying to replicate a complex human condition by dropping mice or rats into inescapable beakers of water is questionable, to say the least!

Even the test results themselves show very high variation with species¹¹ and even between different breeding lines¹².

Scientists themselves are speaking out against the Forced Swim Test due to its lack of merit, published in prominent journals like Nature¹³, The Scientist¹⁴, and called for by international groups like PETA¹⁵ and Humane Research Australia¹⁶.

PETA scientists analysed 30 years (from 1989 to 2018) of publications and identified 47 different test drug compounds that were tested using the Forced Swim Test. 36 of them "showed promise" in the animals. But exactly zero of those are now on the market to treat human depression.¹⁷

In a similar search aimed specifically at pharmaceutical companies, 109 compounds were used in Forced Swim Test experiments by the top 15 pharma companies. Of these, 31 compounds proceeded to human trials, where 15 gave inconclusive results and 9 were clearly not working. Regardless, none of the 7 remaining substances are marketed to treat depression.¹⁸

A groundbreaking study published in the leading scientific journal Nature highlights the need to end the use of mice in cruel depression experiments. Sixty-four researchers worked on analysing the brains of mice and humans. They found substantial species differences in types of brain cells, proportions and the ways they communicate. The authors noted a “magnitude of differences between human and mouse” which would explain the numerous “failures in the use of [the] mouse for preclinical studies”.¹⁹ PETA even built a campaign around this.²⁰