Estrogen and NMDA receptor antagonism: effects upon reference and working memory

Since both estrogen and NMDA receptor antagonists act on the hippocampus CA 1 region and behaviorally affect hippocampal memory tasks, we examined how estrogen depletion (ovariectomy) and NMDA receptor antagonism interact upon spatial memory of the mouse. After ovariectomy or sham operation, mice wer e given a 2-week recovery before behavioral tests began under the influence of vehicle or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ( CPP 2, 5 and 10 mg/kg) intraperitoneal injections. CPP is a competitive, fu ll NMDA receptor antagonist. Spatial reference memory was tested by the wat er maze, spatial working memory was tested by the radial arm maze, while ov erall locomotive activity was monitored by the Y-maze. Results from the wat er maze and the Y-maze did not show any spatial reference memory or activit y differences between sham-operated and ovariectomized mice. The radial arm maze, however, highlighted some working memory differences between intact and ovariectomized mice. CPP treatment impaired dose dependently -the perfo rmance of ovariectomy and sham-operated mice equally on both water maze and radial arm maze, while the drug had no effect on Y-maze performance. These results suggest that short term estrogen deprivation has no effect upon sp atial -reference memory, while it impairs spatial working memory. This effe ct is probably not mediated by NMDA receptors. (C) 1999 Elsevier Science B. V. All rights reserved.