‘Rewilding’ Mice Erases Lab-Induced Anxiety, Challenging Animal research Standards
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A week in the great outdoors can reset the anxious brains of laboratory mice, according to new research, raising essential questions about how we study – and understand – anxiety in animals, and potentially, in humans. The findings suggest that a lack of environmental enrichment, rather than inherent biological factors, may be a primary driver of fear responses observed in lab mice.
Researchers at Cornell University observed that dozens of mice, allowed to roam freely in a large outdoor enclosure, returned to typical anxiety levels after just seven days. This “rewilding” process not only prevented the formation of new fear responses but also appeared to reverse anxiety already developed in a laboratory setting.
The Elevated Plus Maze and the Problem with lab Anxiety
For decades, scientists have relied on tools like the Elevated Plus Maze (EPM) – a tool consisting of two types of arms: enclosed, providing a sense of safety, and exposed, creating a more vulnerable habitat. Typically, mice will cautiously explore the maze, but quickly retreat to the enclosed arms – a behavior interpreted as a sign of anxiety triggered by the open spaces.
Interestingly, this lab-induced anxiety is frequently enough so persistent that it doesn’t respond to common SSRI Anti-Anxiety Drugs – medications commonly used to treat anxiety in humans. This raised concerns among researchers about the validity of the model.
“We put them in the field for a week, and they returned to their original levels of anxiety behavior,” explained a biologist involved in the study. “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.”
The Cornell team freed 44 mice from their cages, allowing them to explore a spacious outdoor environment where they could burrow, climb, and experience a variety of sensations. This proved to be a powerful intervention.Upon returning to the EPM, the mice explored both the open and closed arms equally, behaving as if encountering the maze for the first time.
This effect was observed consistently, irrespective of whether the mice had been raised in a laboratory environment from birth or were introduced to the outdoors later in life. The open field labs where the mice were rewilded are pictured below.
The Importance of Varied Experiences
The research suggests a link between a limited range of experiences and the development of anxiety. A neurobiologist involved in the study explained, “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. 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.”
This concept extends beyond mice, with implications for understanding anxiety in humans. Researchers suggest that a more sheltered life, lacking diverse stimuli, could contribute to heightened anxiety levels. While acknowledging that multiple factors are involved, the study hints that increased exposure to varied – and even risky – experiences might help reduce anxiety.
Rethinking Animal Research and the nature of Anxiety
The findings call for a critical reevaluation of how anxiety is studied in laboratory settings. What appears as inherent anxiety in lab mice may, in fact, be a direct result of their limited environment.
“this opens a lot of possibilities for asking engaging questions about how our library of experiences shapes our response to novel experiences, as I think that’s essentially what anxiety is – when you have an inappropriate response to something that isn’t actually scary,” said a researcher.
The study, published in Current Biology, underscores the importance of considering environmental factors when investigating the biological basis of anxiety and highlights the need for more ecologically valid research models.
