Estrodial effects on age-related shifts in learning and memory: A multiple memory systems approach

Many findings from our lab and others suggest that circulating estrogens as well as estrogen replacement after ovariectomy influence cognitive performance. Young female rats trained during proestrus, when estrogens are high, or with acute estradiol (E2) administration after ovariectomy perform better on the hippocampus-sensitive place task but worse on the striatum-sensitive response task (Korol et al., 2004; Korol and Kolo, 2002). Behavioral neuroscience studies tend to use male rodent models to avoid the complexities of the female reproductive cycle, producing a gap in our knowledge about neural mechanisms of learning and memory in females. As a consequence, age-related effects of estrogens on learning and memory have been poorly characterized despite the fact that women tend to outlive men and may live a substantial portion of their adult life post-menopausally. Our lab recently found that aged male rats shift from a preferred hippocampus-sensitive learning strategy to a striatum-sensitive learning strategy. To better assess estrogen sensitivity in aged female rats, the present study compared the performance of hormonally deprived young (N=17) and aged (N=19) female rats via ovariectomy, with and without estradiol administration on the response task. Rats were given estradiol injections 48 and 24 hrs before training. Young adult rats given the estradiol treatment were slower to acquire the response task though the difference did not reach statistical significance. Aged rats given the estradiol treatment were substantially worse at response learning than were the vehicle-treated rats. These data suggest that estradiol retains its ability to modulate learning and memory well into late age, raising questions about the mechanisms of estradiol action