Novel effects of estradiol and estrogen receptor α and β on cognitive function

Estrogen influences the development of memory function in humans and rodents and can modulate memory in adults. In these studies we examined the role of the estrogen receptors α (ERα) and β (ERβ) in mediating performance on a hippocampal-dependent, hormone-sensitive task, inhibitory avoidance (IA). Ovariectomized (OVX) estrogen receptor-α-knockout (ERαKO) mice displayed impaired performance on the IA task and OVX heterozygotic (HET) mice exhibited performance that was intermediate between ERαKO and wild-type (WT) mice. Impaired performance by ERαKO mice was rescued by E₂ treatment. The ER antagonist, tamoxifen, did not block enhancement of retention by E₂ suggesting that E₂ mediated modulation of memory is not caused by known genomic receptor mechanisms. In contrast to ERαKO mice, IA performance by OVX estrogen receptor-β-knockout (ERβKO) mice was not compromised. The results indicate an important role for ERα, relative to ERβ, in the establishment of cognitive function and suggest that E₂ modulates memory function via a novel estrogenic mechanism. (C) 2000 Elsevier Science B.V.