The current study compared the impact of different paradigms of estradiol replacement on working memory performance. In adult ovariectomized rats, a vehicle-treated control group (n=10) was compared to three estradiol replacement paradigms: 1) continuous delivery via Silastic capsules (n=8); 2) cyclic replacement via two 10 ìg injections on two out of every four days (n=10); 3) cyclic replacement via one 2 ìg injection every four days (n=10). While treatment continued, animals were tested over 24 days in the 8-arm radial maze. After this acquisition period, various delay times were introduced between 4th and 5th arm choices. Treatments had no effects during acquisition or delay trials of 1 min, 10 min, and 3 hours. However, when a 5-hour delay was imposed, rats receiving estradiol via implants outperformed all other groups. These results indicate that long-term continuous estradiol replacement is more effective in enhancing working memory performance than the tested cyclic paradigms
