Letting mice roam freely reverses anxiety, suggesting that results from studies based on laboratory animals may be biased.
Allowing laboratory mice to experience a more natural environment can quickly reverse anxiety-like behaviorsaccording to new research from Cornell University. The revelation calls into question long-held assumptions about how fear develops and is measured in animals and the results of animal studies.
In , published in Current Biology, researchers found that mice released from standard laboratory cages into a large outdoor enclosure returned to baseline levels of anxiety after just one week. The findings suggest that anxiety observed in laboratory settings may be strongly influenced by the environment rather than being a fixed biological characteristic.
“We put them in the field for a week and they returned to their original levels of anxious behavior,” said Matthew Zipple, a biologist at Cornell and one of the study’s authors. “Living in this naturalistic environment blocks the formation of the initial fear response and can reset a fear response which has already been developed in these animals in the laboratory”.
Anxiety in mice is often assessed using the elevated plus maze (EPM), a test consisting of two closed arms and two open, exposed arms elevated above the ground. Rats generally briefly explore the open arms of the maze before returning to the closed areas, a behavior interpreted as fear or anxiety. Notably, this response often persists even after repeated exposure and is resistant to common anxiolytic medications such as SSRIs (Selective Serotonin Reuptake Inhibitors).
In the new study, researchers allowed 44 laboratory rats to roam freely in a spacious outdoor enclosure, where they could dig, climb and experience different weather conditions, textures and stimuli. When the rats were subsequently returned to the elevated plus maze, their behavior has changed drastically. Instead of avoiding open arms, they explored open and closed spaces equally, as if they were encountering the maze for the first time, says .
The effect was consistent regardless of whether the mice were raised outdoors from birth or introduced later, suggesting that even short-term exposure to a richer environment can significantly alter fear responses.
The findings could have broader implications for understanding anxiety in humans. Neurobiologist Michael Sheehan, another study author, said limited experiences can increase anxiety, reducing an individual’s ability to accurately assess threats.
“If you experience a lot of different things every day, you can better calibrate whether something is scary or threatening,” said Sheehan. “But if your experiences are too limited, the novelty itself can trigger anxiety.”
The researchers say the results call for a reevaluation of how anxiety is studied in laboratory animals and how well these models translate to human mental health.
