The influence of sex on activity in voluntary wheel running, forced treadmill running, and open field testing in mice

Physical activity is commonly used for both measuring and treating dysfunction. While preclinical work has been historically biased towards males, the inclusion of both males and females is gaining popularity. With the increasing inclusion of both sexes, it is imperative to determine sex differences in common behavioral assays. This was a secondary analysis of healthy naïve mice to determine baseline sex differences in three activity assays: voluntary wheel running (32 mice), forced treadmill running (178 mice), and open field (88 mice). In voluntary wheel running, females showed greater distance run, running time, bout duration, and speed, but no difference in total bouts. In forced treadmill running, females showed greater time to exhaustion, but no difference in maximum speed attained. In open field, males showed greater active time but no difference in distance and speed over 30 min; however, male mice showed a downward trajectory in distance and speed over the final 20 min of testing, whereas females did not. These data suggest that male mice demonstrate comparable activity intensity to female mice but do not match females' duration of activity, especially for volitional tasks. Researchers utilizing these assays should account for sex differences as they could mask true findings in an experiment.