What Animals Are Tested On For Nimh

Scientists make inferences well-nigh a mouse'southward mental health by measuring the fourth dimension it takes to end swimming. Credit: Philippe Psaila/Science Photo Library

Nearly 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 scout to come across how long information technology tries to stay afloat. In theory, a depressed rodent volition requite upwards more quickly than a happy i — an assumption that has guided decades of enquiry on antidepressants and genetic modifications intended to induce depression in lab mice.

But mental-health researchers have become increasingly sceptical in recent years about whether the forced-swim exam is a good model for depression in people. Information technology is non clear whether mice finish swimming because they are despondent or considering they have learnt that a lab technician will scoop them out of the tank when they cease moving. Factors such as h2o temperature as well seem to affect the results.

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

Now, the animal-rights grouping People for the Ethical Treatment of Animals (PETA) is jumping into the fray. The group wants the U.s.a. National Institute 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 agency on 12 July.

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

"The National Institute of Mental Health has for some fourth dimension been discouraging the employ of certain behavioral assays, including the forced swim and tail suspension test, as models of low," Gordon said in a statement to Nature. "While no single beast test can capture the full complexity of a man disorder, these tests in item are recognized by many scientists equally lacking sufficient mechanistic specificity to be of general use in clarifying the neurobiological mechanisms underlying human low."

Just Gordon said that the tests are still "crucial" for some specific scientific questions, and that the NIMH will continue to fund such studies.

Although scientists insist that behavioural tests that cause stress in animals are necessary for developing human treatments, the PETA entrada dovetails with scientists' growing concern about the quality of data produced by forced-swim tests, says Hanno Würbel, a behavioural biologist at the University of Bern. "The bespeak is that scientists shouldn't use these tests anymore," he says. "In my opinion it'south but bad science."

Sink or swim

Scientists developed the forced-swim examination in the 1970s. One of its primeval applications was studying the efficacy of drugs known as selective serotonin reuptake inhibitors (SSRIs) — a form of antidepressants that includes Prozac (fluoxetine). Mice and rats that received SSRIs swam for longer periods than animals that did not.

The examination'south 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 test as a "quick and dirty" way to appraise their ability to induce low, even though information technology was not designed for that purpose, says Trevor Robbins, a neuroscientist at the University of Cambridge, United kingdom of great britain and northern ireland.

Past 2015, mental-health researchers were publishing an average of ane paper a day that used the procedure, co-ordinate to an analysis by researchers at Leiden University in the Netherlands¹. Still the swim test's rail record is mixed. It has accurately predicted whether unlike SSRIs are effective treatments for depression, but 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 get-go one twenty-four hour period later treatment, whereas in people SSRIs often take weeks or months to reduce symptoms of depression.

Due in part to concerns about the forced-swim examination'due south accuracy, major drug companies such every bit Roche, Janssen and AbbVie take abandoned the process in recent years.

Bobbing along

Many researchers feel obligated to use the test, says Ron de Kloet, a neuroendocrinologist at Leiden University Medical Eye and a co-writer of the 2015 study. "People get their grants based on this test, they write papers based on the test, they make careers," he says. "It'south a civilization which keeps itself alive, 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 test. Just he says the procedure has proved useful for his research into whether the political party drug ketamine and related substances are effective antidepressantsⁱⁱ.

Gould finds information technology ironic that an brute-rights group is attacking the NIMH, because Gordon and several of his predecessors have been outspoken advocates of developing objective biological measures of depression and other mental-wellness disorders. In practical terms, that has meant looking for alternatives to many beast tests. Perhaps unsurprisingly, Gould says that NIMH grant reviewers have tended to push back confronting proposals of his that have included forced-swim tests.

The agency told Nature that it 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 utilise of the animate being proposed is appropriate and justified".

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

She argues that emerging technologies, such as 'mini-brains' grown from human stem cells, could eliminate the need to use rodents in depression studies. Researchers are already using these clumps of human being tissue to study the genetics and encephalon wiring that underlie various mental-health disorders^three.

But some scientists say that the all-time replacement for the forced-swim examination may be more sophisticated tests that involve rodents or other animals. Robbins says that 1 approach could include developing fauna tests that accurately measure out specific symptoms of depression, such as lack of involvement in a favourite food.

And Nestler says that modelling individual signs of low may produce meliorate data than do attempts to mimic the total complexity of the homo disorder in animals. The symptoms and underlying genetics of low seem to vary widely between people, and the aforementioned treatments don't work for everyone.

"We know human being depression is not one disease," he says.

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

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