Spatial working memory learning in young male and female rats: Involvement of different limbic system regions revealed by cytochrome oxidase activity

Sex differences have been found in the spatial memory which involve several regions of the limbic system. The Morris water maze (MWM) is one of the most widely used tasks in behavioral neuroscience to explore spatial and episodic memory in rats. We evaluated the oxidative metabolic activity of the prefrontal cortex, dorsal hippocampus, anterior thalamic nuclei and mammillary region following the acquisition of a spatial working memory (WM) task in young rats (30 days) of both sexes using quantitative histochemistry of the cytochrome oxidase (COx). The rats were trained until they achieved the learning criteria in the MWM using a hidden escape platform with different daily locations, and two control groups were added to evaluate the oxidative metabolism not specific to the learning task. We found a delay in the acquisition of the WM in females. A significant decrease in COx activity was found in the prefrontal cortex in both sexes. Also, changes were found in the dentate gyrus and lateral mammillary nucleus in males, whereas females showed changes in the anterodorsal thalamus and CA3. These results suggest a sex difference in the contribution of brain limbic structures to the WM process during postnatal development.