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

ABSTRACT

Introduction: Physical activity is commonly used for both measuring and treating dysfunction. While preclinical work has been historically biased towards males, the use of both male and female animals is gaining popularity after multiple NIH initiatives. With increasing inclusion of both sexes, it has become imperative to determine sex differences in common behavioral assays. The purpose of this study was to determine baseline sex differences in 3 activity assays voluntary wheel running, forced treadmill running, and open field testing. Methods: This was a secondary analysis of sex differences in healthy mice in 3 different assays Separate mice were used for each assay. Specifically, 16 mice underwent 28 days of voluntary wheel running, 178 mice underwent forced treadmill running, and 88 mice underwent open field testing. Differences between sex across several activity parameters were examined for each assay. Results: In voluntary wheel running, sex differences with larger effect sizes were observed in distance run, running time, and bout duration, with smaller effect size differences in speed, and no difference in total bouts. In forced treadmill running, differences were shown in time to exhaustion, but no difference in max speed attained. In open field, there were sex differences in active time but not in distance and speed in data aggregated over 30 minutes; however, distance and speed in male mice showed a downward trajectory over the final 20 minutes of testing, whereas females maintained the same trajectory. Conclusion: These data suggest that male mice demonstrate comparable activity intensity as female mice but do not match female's duration of activity, especially for volitional tasks. Researchers utilizing these assays should account for sex differences as they could potentially mask true findings in an experiment. Plain English Summary: Physical activity is a common measure to examine function in human subjects with and without disease. Animal models often use measures of physical activity to assess function, yet most of these measures have been done in males only, making interpretation and translation to females and humans difficult. Several measures have been used to measure activity in animals, including those examining voluntary running behavior, maximum capacity, and general activity levels; sex differences between these measures are unclear. We discovered sex differences throughout each of three activity tests. In voluntary running behavior there were large differences between sexes with females running a greater distance and spending more time running. There were small differences in the maximum capacity with females running for a longer period at high intensity. General activity levels showed small differences with females being less active than males. Thus, the greatest differences were found for voluntary running and small differences were found for maximum capacity and general activity levels; differences observed were dependent on the task. Researchers utilizing these assays should account for sex differences as they could potentially mask true findings in an experiment.