Contribution of sex differences in the acute stress response to sex differences in water maze performance in the rat

Male rats outperform females in spatial tasks, such as the water maze (WM). Female rats are known to have higher basal serum corticosterone (CORT) levels and to manifest a more rapid and stronger CORT response to novel stressors. Sex differences in stress responses to the handling and forced swimming in the WM task might contribute to the sex difference in WM performance. In Experiment 1, naive females were found to be impaired relative to naive males in swimming to a visible platform in a WM pool due to strongly thigmotaxic swimming by females. In Experiment 2, serum CORT, a physiological measure of stress, was highly elevated during and after WM training, with female > male values and strong inverse correlations between CORT and measures of WM performance in females. Familiarization with the WM pool and test procedures by strategies pretraining prior to spatial training reduced or eliminated the sex differences in the stress response and WM performance. In Experiment 3, adrenalectomy to eliminate the stress response eliminated sex differences in WM performance. Taken together, the results suggest that male and female rats may harbor brain circuitry that is equally capable of accurate spatial navigation and memory in the WM but which may be impaired to different degrees by the differential stress responses triggered by WM testing.