Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Amy Arnsten


The present study was conducted to determine the effect of differential endogenous estrogen exposure in rats on stress-induced changes in spatial working memory. Subjects comprised male (n=8) and female (n=10) Sprague-Dawley rats, which were trained to complete a T maze, delayed alternation task. Performance was scored as a percentage of trials during which the correct maze arm was selected. Subjects scores were recorded after 1 and 2 hours of restraint stress, as well as after 1 hour of unimpeded movement in a cage placed in the testing room. Restraint stress was effected through physical confinement within plastic, cylindrical tubing. Female subjects underwent each of the testing conditions twice, during periods of high and low endogenous estrogen exposure, as ascertained by microscopic examination of vaginal epithelial cells for estrous cycle stage determination. Females in proestrus (elevated endogenous estrogen exposure) subjected to 1 hour of restraint performed significantly worse than their baseline scores (p=0.0017) or females in estrus (low endogenous estrogen exposure) after 1 hour of restraint (p=0.00014). After 1 hour of restraint, females in proestrus also committed an increased rate of perseverative errors compared to females in estrus, although this increase did not achieve statistical significance (p=0.06). No appreciable differences existed among subject groups in baseline performance or subsequent to 2 hours of restraint stress. Resultant data indicate impaired working memory among female rats under conditions of stress in the context of elevated endogenous estrogen exposure. This study, then, suggests a potential synergistic effect of stress and estrogen in compromising prefrontal cortex function and, therefore, may lend insight into the observed sex-related disparity in the incidence of major depressive disorder and other anxiety-related mood disorders.