Are there sex differences in spatial reference memory in the Morris water maze? A large-sample experimental study

Sex differences have been found in allocentric spatial learning and memory tasks, with the literature indicating that males outperform females, although this issue is still controversial. This study aimed to explore the behavior of male and female rats during the habituation and learning of a spatial memory task performed in the Morris Water Maze (MWM). The study included a large sample of 89 males and 85 females. We found that females searched slightly faster than males during habituation with a visible platform. During learning, both male and female rats decreased the latency and distance traveled to find the hidden platform over the days, with males outperforming females in the distance traveled. Females swam faster but did not find the platform earlier, suggesting a less directed navigational strategy. Both sexes increased time spent in the target zone over the days, with no sex differences. Although females swam more in the periphery during the first days of the task, both sexes decreased the time spent in this area. Finally, only males increased swimming in the pool's center over the days, spending more time than females in this area across the entire training. In conclusion, we need to register several variables in the MWM and analyze path strategies to obtain more robust results concerning sex differences. Research on spatial learning should include both sexes to achieve a more equitable, representative, and translational science.