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

Heather N. Fugger, Thomas C. Foster, Jan Åke Gustafsson, Emilie F. Rissman

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)258-264
Number of pages7
JournalBrain Research
Issue number2
StatePublished - Nov 17 2000


  • Aging
  • Inhibitory avoidance
  • Learning and memory
  • Steroid hormone receptors

ASJC Scopus subject areas

  • Neuroscience(all)


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