Sex differences in learning and memory in mice: effects of sequence of testing and cholinergic blockade

Sexual dimorphism in spatial and cued navigation using the Morris water maze was examined in C57BL/6 mice both with and without administration of scopolamine, a cholinergic blocker. In Exp. 1, female and male mice learned to perform first a spatial, then a cued, navigation task. Both performed a spatial task similarly; males, however, performed a cued task better than females. In Exp. 2, the sequence of navigation testing was reversed. Both performed similarly on a cued task; however, males performed a spatial task better than females. In both experiments, females were more sensitive than males to the effects of scopolamine. No significant confounding sex differences were found in either spontaneous activity or passive avoidance retention. These data indicate that sex differences in spatial and cued tasks are dependent on the sequence of task presentation and implicate a role for the cholinergic system in these differences.