Depression researchers reconsider popular mouse swim exams

Nearly every scientist who has used mice or rats to examine melancholy is acquainted with the forced-swim check. The animal is dropped right into a tank of water simultaneously as researchers watch to peer how long it tries to live afloat. In concept, a depressed rodent will give up greater speedy than a happy one — an assumption that has guided a long time of research on antidepressants and genetic modifications intended to induce melancholy in lab mice.

Depression researchers reconsider popular mouse swim exams 1
But mental-health researchers have ended up increasingly skeptical in current years about whether the pressured-swim check is a superb version for depression in humans. It is not clear whether mice stop swimming because they are despondent or have learned that a lab technician will scoop them out of the tank after they prevent shifting. Factors that include water temperature also appear to affect the consequences.
“We don’t realize what despair looks as if in a mouse,” says Eric Nestler, a neuroscientist on the Icahn School of Medicine at Mount Sinai in New York City.

Now, the animal-rights organization People for the Ethical Treatment of Animals (PETA) leaps into the fray. The group needs the American National Institute of Mental Health (NIMH) in Bethesda, Maryland, to prevent supporting using the compelled-swim test and similar behavioral assessments via its personnel and furnish recipients. The checks “create intense worry, tension, terror, and depression in small animals” without providing useful statistics, PETA stated in a letter to the company on 12 July.
The animal-rights organization additionally singled out NIMH director Joshua Gordon to use the pressured-swim take a look at in the early 2000s, when he changed into a researcher at Columbia University in New York City.

“The National Institute of Mental Health has for some time been discouraging the usage of certain behavioral assays, such as the compelled swim and tail suspension test, as models of depression,” Gordon said in an announcement to Nature. “While no single animal test can seize the total complexity of a human ailment, these exams particularly are recognized by using many scientists as missing enough mechanistic specificity to be of preferred use in clarifying the neurobiological mechanisms underlying human depression.”
But Gordon said that the exams are nonetheless “vital” for a few precise scientific questions and that the NIMH will continue to fund such research.

Although scientists insist that behavioral exams that purpose pressure in animals are necessary for growing human remedies, the PETA campaign dovetails with scientists’ growing challenge approximately the excellent statistics produced through pressured-swim checks, says Hanno Würbel, a behavioral biologist at the University of Bern. “The factor is that scientists shouldn’t use those checks anymore,” he says. “In my opinion, it’s just bad science.”

Sink or swim

Scientists evolved the forced-swim take a look at within the 1970s. One of its earliest programs changed into analyzing the efficacy of drugs referred to as selective serotonin reuptake inhibitors (SSRIs) — a category of antidepressants that includes Prozac (fluoxetine). Mice and rats that acquired SSRIs swam for longer intervals than animals that did now not.

The test’s reputation grew within the early 2000s, while scientists started out enhancing mouse genomes to mimic mutations connected to despair in people. Many of those researchers adopted the forced-swim take a look at as a “brief and dirty” manner to assess their capacity to induce melancholy, even though it becomes no longer designed for that purpose, says Trevor Robbins, a neuroscientist at the University of Cambridge, UK.
By 2015, mental-health researchers had been publishing an average of one paper an afternoon that used the process, consistent with an evaluation through researchers at Leiden University within the Netherlands1. Yet the swim test’s tune record is blended. It should be expected whether one-of-a-kind SSRIs are effective treatments for depression, however, yields inconsistent outcomes when used with other types of antidepressant.

And some factors of the SSRI outcomes are puzzling. Mice given the drugs display measurable changes in behaviour in the course of swim exams beginning at some point after remedy. In humans, SSRIs regularly take weeks or months to lessen symptoms of melancholy.
Due to concerns about the forced-swim check’s accuracy, primary drug corporations, including Roche, Janssen, and AbbVie, have abandoned the process in current years.

Bobbing along

Many researchers feel obligated to use the test, says Ron de Kloet, a neuroendocrinologist at Leiden University Medical Center and a co-writer of the 2015 study. “People get their grants based on this check, they write papers primarily based at the check, they make careers,” he says. “It’s a subculture which continues itself alive, despite the fact that maximum of them will admit that the exams are not showing what they are purported to do.”
Todd Gould, a neurobiologist at the University of Maryland School of Medicine in Baltimore, acknowledges the negative song report of the compelled-swim check. But he says the method has proved beneficial for his studies into whether the party drug ketamine and associated substances are powerful antidepressants2.

Gould reveals it ironic that an animal-rights institution is attacking the NIMH due to the fact Gordon and several of his predecessors were outspoken advocates of growing goal organic measures of depression and other intellectual-health issues. In practical terms, that has intended looking for options to many animal exams. Perhaps unsurprisingly, Gould says that NIMH provides reviewers have tended to thrust back against proposals of his that have included forced-swim tests.

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