II. Cognitive performance of middle-aged female rats is influenced by capacity to metabolize progesterone in the prefrontal cortex and hippocampus

Abstract

Cognitive decline can occur with aging; however, some individuals experience less cognitive decline than do others. Secretion of ovarian hormones is reduced post-menopause and may contribute to cognitive function. The extent to which hormonal effects may be parsed out from other age-related factors to influence cognition is of interest. Middle-aged (12-month-old) female rats that were retired breeders were categorized as maintaining or declining reproductive function based upon their estrous cyclicity (regular 4–5 day cycles), fertility (> 60 % successful pregnancy), and fecundity (> 10 pups/litter). Performance in object recognition, Y-maze, water maze, inhibitory avoidance, and contextual–cued fear conditioning was evaluated. Estradiol, progesterone (P 4), dihydroprogesterone, and 5α-pregnan-3α-ol-20-one (3α,5α-THP) were assessed in medial prefrontal cortex (mPFC) and hippocampus; corticosterone was assessed in plasma. Rats maintaining reproductive function performed significantly better on the object recognition, Y-maze, water maze, inhibitory avoidance, and cued fear conditioning tasks than did rats with declining reproductive function. Steroid concentrations varied greatly within groups. Higher levels of P 4 in mPFC and hippocampus were associated with better Y-maze performance. In mPFC, higher levels of P 4 were associated with poorer inhibitory avoidance performance; greater levels of 3α,5α-THP were associated with better object memory. Neither estradiol nor corticosterone levels significantly contributed to cognitive performance. Thus, the capacity for cortico-limbic P 4 utilization may influence cognitive performance in aging.