What Animals Do They Test On Nimh

Scientists make inferences about a mouse's mental wellness by measuring the time information technology takes to stop pond. Credit: Philippe Psaila/Science Photo Library

Most every scientist who has used mice or rats to study depression is familiar with the forced-swim test. The animal is dropped into a tank of water while researchers watch to meet how long information technology tries to stay afloat. In theory, a depressed rodent volition surrender more than apace than a happy 1 — an assumption that has guided decades of research on antidepressants and genetic modifications intended to induce depression in lab mice.

But mental-wellness researchers have become increasingly sceptical in recent years about whether the forced-swim exam is a good model for low in people. Information technology is non clear whether mice end swimming because they are despondent or because they have learnt that a lab technician will scoop them out of the tank when they cease moving. Factors such every bit water temperature also seem to affect the results.

"We don't know what depression looks like in a mouse," says Eric Nestler, a neuroscientist at the Icahn School of Medicine at Mount Sinai in New York Metropolis.

Now, the brute-rights grouping People for the Ethical Handling of Animals (PETA) is jumping into the fray. The group wants the US National Found of Mental Health (NIMH) in Bethesda, Maryland, to stop supporting the use of the forced-swim test and similar behavioural assessments by its employees and grant recipients. The tests "create intense fear, anxiety, terror, and depression in small animals" without providing useful data, PETA said in a letter to the bureau on 12 July.

The creature-rights group likewise singled out NIMH director Joshua Gordon for using the forced-swim test in the early 2000s, when he was a researcher at Columbia Academy in New York City.

"The National Institute of Mental Health has for some time been discouraging the apply of certain behavioral assays, including the forced swim and tail suspension test, as models of depression," Gordon said in a statement to Nature. "While no single animate being examination tin capture the full complexity of a human disorder, these tests in detail are recognized by many scientists as defective sufficient mechanistic specificity to be of general utilize in clarifying the neurobiological mechanisms underlying human depression."

But Gordon said that the tests are nonetheless "crucial" for some specific scientific questions, and that the NIMH will proceed to fund such studies.

Although scientists insist that behavioural tests that cause stress in animals are necessary for developing human treatments, the PETA campaign dovetails with scientists' growing business organization nigh the quality of data produced by forced-swim tests, says Hanno Würbel, a behavioural biologist at the University of Bern. "The point is that scientists shouldn't use these tests anymore," he says. "In my opinion it'due south just bad scientific discipline."

Sink or swim

Scientists developed the forced-swim test in the 1970s. I of its earliest applications was studying the efficacy of drugs known every bit selective serotonin reuptake inhibitors (SSRIs) — a class of antidepressants that includes Prozac (fluoxetine). Mice and rats that received SSRIs swam for longer periods than animals that did non.

The examination's popularity grew in the early 2000s, when scientists began modifying mouse genomes to mimic mutations linked to depression in people. Many of these researchers adopted the forced-swim examination as a "quick and dirty" way to assess their ability to induce depression, even though it was not designed for that purpose, says Trevor Robbins, a neuroscientist at the University of Cambridge, Great britain.

By 2015, mental-health researchers were publishing an average of one paper a twenty-four hours that used the process, according to an assay past researchers at Leiden University in kingdom of the netherlands¹. Withal the swim test's track record is mixed. It has accurately predicted whether different SSRIs are effective treatments for depression, only yields inconsistent results when used with other types of antidepressant.

And some aspects of the SSRI results are puzzling. Mice given the drugs show measurable changes in behaviour during swim tests beginning one day subsequently treatment, whereas in people SSRIs often have weeks or months to reduce symptoms of depression.

Due in part to concerns near the forced-swim test's accuracy, major drug companies such as Roche, Janssen and AbbVie take abandoned the procedure in recent years.

Bobbing along

Many researchers experience obligated to utilise the test, says Ron de Kloet, a neuroendocrinologist at Leiden Academy Medical Center and a co-author of the 2015 report. "People become their grants based on this exam, they write papers based on the exam, they make careers," he says. "It'south a culture which keeps itself live, even though most of them will admit that the tests are not showing what they are supposed to do."

Todd Gould, a neurobiologist at the University of Maryland School of Medicine in Baltimore, acknowledges the poor track record of the forced-swim examination. But he says the procedure has proved useful for his research into whether the party drug ketamine and related substances are effective antidepressants².

Gould finds it ironic that an animate being-rights grouping is attacking the NIMH, because Gordon and several of his predecessors have been outspoken advocates of developing objective biological measures of low and other mental-health disorders. In practical terms, that has meant looking for alternatives to many animal tests. Perhaps unsurprisingly, Gould says that NIMH grant reviewers have tended to push back against proposals of his that take included forced-swim tests.

The bureau told Nature that information technology requires grant applicants to supply written justification for using animals in research, and that its review system "evaluates these descriptions very rigorously to determine whether the employ of the brute proposed is appropriate and justified".

Emily Trunnell, a inquiry associate at PETA's Laboratory Investigations Department in Norfolk, Virginia, says that the group decided to target the NIMH because of the agency's prominence in mental-health research. "We believe that if NIMH took a stand up, it would set a stiff precedent," she says.

She argues that emerging technologies, such as 'mini-brains' grown from human stalk cells, could eliminate the need to apply rodents in depression studies. Researchers are already using these clumps of human tissue to report the genetics and brain wiring that underlie various mental-health disordersⁱⁱⁱ.

But some scientists say that the best replacement for the forced-swim test may be more than sophisticated tests that involve rodents or other animals. Robbins says that one arroyo could include developing animal tests that accurately measure specific symptoms of low, such as lack of interest in a favourite food.

And Nestler says that modelling individual signs of low may produce better data than do attempts to mimic the full complication of the human disorder in animals. The symptoms and underlying genetics of depression seem to vary widely between people, and the same treatments don't piece of work for everyone.

"We know human depression is not ane affliction," he says.

Source: https://www.nature.com/articles/d41586-019-02133-2

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