Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats

Jazmin I. Acosta, Loretta Mayer, Joshua S. Talboom, Cynthia Zay, Melissa Scheldrup, Jonathan Castillo, Laurence M. Demers, Craig K. Enders, Heather Bimonte-Nelson

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 μg), CEE-Medium (20 μg) or CEE-High (30 μg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 β-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.

Original languageEnglish (US)
Pages (from-to)454-464
Number of pages11
JournalHormones and Behavior
Volume55
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Estrogen
  • Hormone replacement
  • Learning
  • Reference memory
  • Spatial memory
  • Working memory

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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