Stress-induced corticosterone secretion covaries with working memory in aging

A substantial literature details the relationship between age-related changes to the hypothalamic-pituitary-adrenal axis and deterioration of mnemonic functions that depend on the hippocampus. The relationship between adrenocortical status and other forms of memory that depend on the prefrontal cortex is less well understood in the context of advanced age. Here, we characterized performance of young adult and aged F344 rats on a prefrontal cortex-dependent working memory task and subsequently measured corticosterone (CORT) levels over the diurnal cycle and during exposure to an acute stressor. Our analyses revealed that aged rats with better working memory mounted a greater CORT response during acute stress exposure than either young adults or age-matched rats with impaired working memory. We also observed that age-related elevation of basal CORT levels is not associated with working memory performance. Jointly, these data reveal that the hypothalamic-pituitary-adrenal axis-mediated response to acute stress is positively associated with working memory in aging.