Novel effects of estradiol and estrogen receptor alpha and beta on cognitive function

Estrogen influences the development of memory function in humans and rodent s and can modulate memory in adults. In these studies we examined the role of the estrogen receptors alpha (ER alpha) and beta (ER beta) in mediating performance on a hippocampal-dependent, hormone-sensitive task, inhibitory avoidance (I4). Ovariectomized (OVX) estrogen receptor-alpha -knockout (ER alpha KO) mice displayed impaired performance on the IA task and OVX hetero zygotic (HET) mice exhibited performance that was intermediate between ER a lpha KO and wild-type (WT) mice. Impaired performance by ER alpha KO mice w as rescued by E-2 treatment. The E-2 antagonist, tamoxifen, did not block e nhancement of retention by E-2 suggesting that E-2 mediated modulation of m emory is not caused by known genomic receptor mechanisms. In contrast to ER alpha KO mice, IA performance by OVX estrogen receptor-beta -knockout (ER beta KO) mice was not compromised. The results indicate an important role f or ER alpha, relative to ER beta in the establishment of cognitive function and suggest that E-2 modulates memory function via a novel estrogenic mech anism. (C) 2000 Elsevier Science B.V. All rights reserved.