An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour

Behavioural tests to assess affective states are widely used in human research and have
recently been extended to animals. These tests assume that affective state influences cognitive
processing, and that animals in a negative affective state interpret ambiguous information
as expecting a negative outcome (displaying a negative cognitive bias). Most of
these tests however, require long discrimination training. The aim of the study was to validate
an exploration based cognitive bias test, using two different handling methods, as previous
studies have shown that standard tail handling of mice increases physiological and
behavioural measures of anxiety compared to cupped handling. Therefore, we hypothesised
that tail handled mice would display a negative cognitive bias. We handled 28 female
CD-1 mice for 16 weeks using either tail handling or cupped handling. The mice were then
trained in an eight arm radial maze, where two adjacent arms predicted a positive outcome
(darkness and food), while the two opposite arms predicted a negative outcome (no food,
white noise and light). After six days of training, the mice were also given access to the
four previously unavailable intermediate ambiguous arms of the radial maze and tested for
cognitive bias. We were unable to validate this test, as mice from both handling groups displayed
a similar pattern of exploration. Furthermore, we examined whether maze exploration
is affected by the expression of stereotypic behaviour in the home cage. Mice with
higher levels of stereotypic behaviour spent more time in positive arms and avoided ambiguous
arms, displaying a negative cognitive bias. While this test needs further validation, our
results indicate that it may allow the assessment of affective state in mice with minimal training—
a major confound in current cognitive bias paradigms.