Estrogen modulates place learning through estrogen receptors in the hippocampus

Lilia Zurkovsky, Stephanie L. Brown, Donna L. Korol

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Moderate elevations in circulating estradiol enhance learning in tasks that tap place learning strategies such as those requiring the use of extramaze cues. Use of place learning strategies is particularly impaired by damage to the hippocampus, a structure shown to be sensitive to estrogen treatments. We have shown that direct estrogen infusions into the dorsal hippocampus, and not the dorsolateral striatum, enhance place learning, suggesting that the hippocampus may be an important modulatory site for the effects of estrogen on place learning. The current experiment tested whether the hippocampus is indeed a critical site of estrogen modulation through classical estrogen receptors. Young adult female Sprague-Dawley rats were ovariectomized for 21 days and given systemic injections (0.1 ml) of sesame oil (OIL) or 10 μg of 17β-estradiol-benzoate (E2), 48 and 24 h before being trained on a place task. Twenty-four hours prior to the first systemic injection, separate groups of rats received bilateral hippocampal implants of either the antiestrogen ICI 182,780 (ICI) or cholesterol vehicle. Implants were maintained until and throughout training. Intrahippocampal ICI reversed the enhancement in place learning seen with systemic E2 treatment. Unexpectedly, intrahippocampal ICI in OIL-treated rats also enhanced place learning. These data suggest that ICI may have some mixed agonist and antagonist effects in the hippocampus and that estrogen enhances place learning through activation of estrogen receptors located in the hippocampus.

Original languageEnglish (US)
Pages (from-to)336-343
Number of pages8
JournalNeurobiology of Learning and Memory
Issue number3
StatePublished - Nov 2006
Externally publishedYes


  • Antiestrogen
  • Estradiol
  • Female
  • ICI 182,780
  • Learning strategy
  • Memory systems
  • Spatial
  • Steroids

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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