Researchers observed that dozens of laboratory mice allowed to roam in large outdoor enclosures returned to mouse-typical anxiety levels after just a week, suggesting that “rewilding” may prevent the development of laboratory-induced fear responses in the first place.
Cornell University researchers say their findings raise questions about the best way to test anxiety in animals in the laboratory. This could also give us a sense of how anxiety begins to develop in animals (including ourselves).
“We put them in the wild for a week, and they returned to their old levels of anxious behavior,” said biologist Matthew Zipper.
“Living in this natural environment can both prevent the development of the initial fear response and reset the fear response that has been developed in these animals in the laboratory.”
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Researchers commonly use the elevated plus maze, or EPM, to induce and measure anxiety in mice. It has two arms: a closed arm, which makes the animal feel safer, and an exposed arm, which keeps the mouse in a more open environment.
In a standard response to EPM, mice tend to explore the maze before returning to the enclosed space. This was interpreted as a sign of fear triggered by a single exposure to an open area, a behavior so persistent that it became resistant to SSRI anti-anxiety medications.
When researchers released 44 mice from their laboratory cages to explore a relatively large outdoor space, burrowing, climbing and experiencing a variety of different sensations and conditions, they found that it acted like a reset button.
An open-air laboratory where rats are reintroduced. (Chris Kitchen/Cornell University)
Mice returning to the EPM similarly explored open and closed spaces as if encountering the maze for the first time. This effect was observed regardless of whether the mice were feraled from birth.
These findings may have implications for how we understand anxiety and its relationship to the environment—and this may be true for both humans and mice. A small number of experiences may trigger anxiety.
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“If you experience a lot of different things every day, you have better ways of calibrating whether something is scary or threatening,” says neurobiologist Michael Sheehan.
“But if you’ve only had it five times, then you have a sixth experience and it’s very different from everything you’ve done before, and that’s anxiety-provoking.”
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The researchers suggest that it may be necessary to rethink how anxiety is studied in the laboratory and how experiments in mice can be applied to humans. What we think of as anxiety in lab mice may be easily mitigated by their environment, rather than being innate.
Research has also explored the idea that this more sheltered life can lead to anxiety. Perhaps more varied and even risky experiences can help reduce anxiety – although we also know there are multiple factors involved.
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“This opens up a lot of possibilities for asking interesting questions about how our experience repertoire affects our response to novel experiences, because I think that’s essentially what anxiety is—when you react inappropriately to things that aren’t actually scary,” Sheehan said.
The study was published in modern biology.