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 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 heterozygotic (HET) mice exhibited performance that was intermediate between ER alpha KO and wild-type (WT) mice. Impaired performance by ER alpha KO mice was rescued by E-2 treatment. The E-2 antagonist, tamoxifen, did not block enhancement of retention by E-2 suggesting that E-2 mediated modulation of memory 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 for ER alpha, relative to ER beta in the establishment of cognitive function and suggest that E-2 modulates memory function via a novel estrogenic mechanism. (C) 2000 Elsevier Science B.V. All rights reserved.