Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling

Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have revealed that picking up laboratory mice by the tail induces aversion, anxiety, physiological stress and depression-like behaviour, but such negative responses can be reduced substantially by using a handling tunnel that mice enter readily with minimal familiarisation. It has not been tested whether anxiety and aversion can be reduced similarly by using other objects to lift up mice from their home cage. Here we compared the willingness of C57BL/6NRj mice to interact voluntarily with their handler after being picked up either on a plastic ladder present in the home cage, or inside a familiar tunnel, or lifted by the base of the tail and then returned to the home cage. We also tested anxiety in open field and elevated plus maze tests once animals were familiarised with their assigned handling method. While mice picked up briefly by the tail were unwilling to interact with the hand that picked them up, mice picked up by ladder or tunnel readily approached, climbed on or entered these devices, with no significant difference in time spent with ladder or tunnel. Anxiety in an unfamiliar open field was reduced to a similar extent in ladder and tunnel handled mice compared with those picked up by the tail. Mice handled by tunnel also showed reduced anxiety in an elevated plus maze compared to those handled by tail, while ladder handling resulted in an intermediate response. Our study shows that, like tunnels, using home cage ladders to pick up mice reduces anxiety and avoids the aversion that is induced by picking up mice by their tails. We discuss the potential practicality of using ladders and tunnels to handle mice in different contexts.