Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze.

Previous investigations of estradiol's effects on learning and memory yielded equivocal results. This study was designed to determine whether these inconsistencies were due to dose-dependent effects of estradiol on different memory processes. Ovariectomized female rats were injected daily with estradiol benzoate (EB; 0.32, 1.00, or 5.00 microg) or vehicle. Approximately 3 hr after injection, rats were run on a hippocampus-dependent working/reference memory version of the radial arm maze. Total number of working (WME), reference, and combined working/reference memory errors were scored. Compared with vehicle, 1.00 or 5.00 microg EB (high physiological) impaired performance by increasing the number of WME, whereas 0.32 microg EB (low physiological) facilitated performance by decreasing the number of WME. Taken together, these data demonstrate a dose-dependent effect of EB on working memory.