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

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.