Sexually dimorphic cognitive style, female sex hormones, and cortical nitric oxide

Recent studies using the water maze (WM) found marked sex differences in behavioral strategy employed in place learning tasks in adult rats. When a change in the platform position is introduced following learning the place of a platform (visible or hidden) in a different position, female rats escape to the newly positioned visible platform faster than males. Nitric oxide (NO) is implicated in place learning, and there are regional sex differences in its stable metabolites, NO(2)(-)+NO(3)(-), in rat brain. Furthermore, NO(2)(-)+NO(3)(-) levels are sensitive to ovariectomy in female rats. The effect of sex hormones on brain development and function is well documented. The present study was undertaken to study the effects of ovariectomy and hormonal manipulations on cognitive performance in a WM task designed to test differences in behavioral strategy in Sprague-Dawley rats (n=48) of both sexes. Some of the females rats were ovariectomised and received either hormone replacement (estrogen or progesterone alone or in combination) or the vehicle. Cortical and hippocampal NO(2)(-)+NO(3)(-) levels were determined after behavioral testing. There were no group differences in cognitive ability or non-cognitive factors such as motivation or swim speed. Males and intact females differed in their cognitive style, but hormonal manipulations in female rats did not affect this relative use of behavioral strategy. There was a correlation between performance on the trial where sex differences were most prominent and NO(2)(-)+NO(3)(-) levels in the cortex. Our results suggest that the activational effects of circulating gonadal hormones do not play a major role in sexually dimorphic cognitive styles.