Hurst, J. L., West, R. S. 2010. Taming anxiety in laboratory mice. Nature Methods 7(10), 825-826.

Handling experience (which includes routine maintenance) can have positive or negative effects on stress responses that influence experiments, depending on the animals' experience during handling. The most common method used to capture and handle laboratory mice is to pick up and restrain the mouse by its tail. However, we show here that this induces a high level of anxiety and mice do not readily habituate to handling by this method. Even after multiple handling sessions, mice picked up by the tail avoided voluntary approach of a handler, showed a high level of urination and defecation during handling, and showed high levels of anxiety in an elevated plus maze test. By contrast, mice picked up either using a tunnel present in the home cage, or cupped on the open hands, quickly developed much higher levels of voluntary interaction with a handler, showed low levels of urination and defecation during handling, and low levels of anxiety in an elevated plus maze test. These responses generalised across different strains and sexes of mice, and across handlers with differing levels of experience. These notable differences in responses may not have been recognised previously because picking up mice by the tail is so widely used in laboratories that the aversive and anxious response is perceived as normal. However, use of methods that do not induce strong anxiety responses will minimize confounding responses due to routine handling before and during experiments. In addition to providing more robust scientific outcomes, appropriate choice of handling method could enhance the welfare of the many millions of mice that are housed and handled in laboratories worldwide.