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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.

The present study investigated the role of endogenous opioids in the expression of defensive behaviors (DBs) and the suppression of cell proliferation (CP) in the dentate gyrus (DG) induced by exposure to predator odor, trimethyl thiazoline (TMT). Adult male rats were injected with either naltrexone (an opioid antagonist, 5 mg/kg) or saline 30 min before exposure to either TMT or a control odor. Behavior was scored for the first 15 min of odor exposure. Bromodeoxyuridine (BrdU, 200 mg/kg) was then injected, and the rats were perfused 1 hr later. Exposure to TMT increased the expression of DBs and suppressed the number of proliferating cells in the DG. Pretreatment with naltrexone attenuated the effects of TMT on DB expression but did not attenuate the effects of TMT on CP. In addition, naltrexone administration suppressed CP in the absence of TMT. These results demonstrate a dissociation between DBs and regulation of CP in the DG.