Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition

Horm Behav. 1999 Dec;36(3):222-33. doi: 10.1006/hbeh.1999.1541.


A delayed matching-to-position (DMP) T-maze task was used to examine the effects of estrogen replacement on spatial learning and memory, as well as the ability of estrogen replacement to reduce performance deficits produced by acute systemic and intrahippocampal muscarinic cholinergic inhibition. Two experiments were performed. In Experiment 1, ovariectomized animals were trained to criterion on the DMP task and then tested with increased intertrial delays and following systemic scopolamine administration. The animals then received either continuous estrogen replacement or sham surgery and were retested beginning 10 days later. In Experiment 2, ovariectomized animals received guide cannulae implanted bilaterally into the hippocampus. Half of these animals also began receiving continuous estrogen replacement. Two months later, the animals were trained on the DMP task and then tested with increased intertrial delays and following systemic as well as intrahippocampal scopolamine administration. Animals received the same test battery 8 months later and were then immediately trained on a reversal task. The results indicate that estrogen-treated animals acquired the DMP task at a significantly faster rate than the ovariectomized, non-estrogen-treated controls. In addition, estrogen replacement significantly reduced deficits in DMP performance produced by intrahippocampal, but not systemic, scopolamine administration. This occurred when animals were tested after 3.5 months, as well as after 12 months, of continuous estrogen replacement. No evidence for an effect of estrogen replacement on spatial working memory or reversal learning was detected. These findings demonstrate that estrogen replacement can enhance acquisition of a spatial memory task and reduce performance deficits associated with hippocampal cholinergic impairment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Estradiol / pharmacology
  • Estrogen Replacement Therapy*
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects*
  • Memory / physiology
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / pharmacology*
  • Ovariectomy
  • Pilot Projects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / metabolism*
  • Retention, Psychology / drug effects
  • Retention, Psychology / physiology
  • Scopolamine / administration & dosage
  • Scopolamine / pharmacology
  • Space Perception / drug effects*
  • Space Perception / physiology
  • Time Factors


  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Estradiol
  • Scopolamine