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Dozens of laboratory mice allowed to roam a large outdoor enclosure returned to a typical level of mouse anxiety after just one week, researchers observed, suggesting that ‘rewilding’ may prevent lab-induced fear responses from developing in the first place.
The researchers, from Cornell University in the US, say their findings raise questions about the best ways to run anxiety tests on animals in the lab. This could also teach us something about how anxieties first begin to form in animals, including ourselves.
“We put them in the field for a week, and they returned to their original levels of anxiety behavior,” says biologist Matthew Zipple.
“Living in this naturalistic environment both blocks the formation of the initial fear response, and it can reset a fear response that’s already been developed in these animals in the lab.”
Related: Scientists Identify Neurons Driving Anxiety – And How to Calm Them
Researchers typically induce and measure anxiety in mice using what’s called an elevated plus maze or EPM. It has two arms: an enclosed arm, which makes the animals feel safer, and an exposed arm, where the mice are in a more open environment.
In a standard response to the EPM, mice tend to explore the maze before returning to the enclosed spaces. This is interpreted as a sign of fear triggered by a single exposure to the open areas, a behavior so persistent that it resists SSRI anti-anxiety drugs.
When researchers freed 44 mice from their lab cages to explore a relatively vast space outdoors, to burrow and climb and experience a variety of different sensations and conditions, they found it acted like a reset button.
Mice that were returned to the EPM explored both the open and closed spaces equally, as if encountering the maze for the first time. The effects were observed across mice regardless of whether they were rewilded from birth or not.
The findings may have implications for how we understand anxiety and its relationship to our environment – something that may be true of people as well as mice. It’s possible that a narrow set of experiences can drive anxiety.
“If you experience lots of different things that happen to you every day, you have a better way to calibrate whether or not something is scary or threatening,” says neurobiologist Michael Sheehan.
“But if you’ve only had five experiences, you come across your sixth experience, and it’s quite different from everything you’ve done before, that’s going to invoke anxiety.”
The researchers suggest a rethink might be needed about how anxiety is studied in the lab, and how applicable experiments with mice could be to humans. What we think of as anxiety in lab mice might be easily mitigated by their environment, rather than being hardwired into their biology.
This idea of a more sheltered life as a contributor to anxiety is something that’s been explored in studies of people as well. Perhaps more varied and even more risky experiences could help reduce anxiety – though we also know that there are multiple factors involved.
“This opens a lot of possibilities for asking interesting questions about how our library of experiences shapes our response to novel experiences, because I think that’s essentially what anxiety is – when you have an inappropriate response to something that isn’t actually scary,” says Sheehan.
The research has been published in Current Biology.
