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Dose-dependent effects of estradiol on working memory and the phosphorylation of cAMP response element-binding protein Sinopoli, Katia Joanne


Estradiol can influence a variety of physiological and psychological processes. This hormone has been shown to influence learning and memory processes. The effects of physiological levels of estradiol on spatial working memory performance were explored in Chapter 1. In Experiment 1, daily systemic estradiol or oil injections were administered to adult, ovariectomized female rats approximately 4 hours prior to the testing on a win-shift version of the radial arms maze. A high dose of estradiol (5 μg estradiol benzoate) enhanced acquisition of the task whereas a low dose (0.3 μg estradiol benzoate) impaired working memory performance. Experiment 2 was conducted to examine site-specific influences of estradiol on spatial working memory in well-trained rats. Saline and two doses of estradiol cyclodextrin (0.1 μg and 0.9 μg estradiol/0.5 μL saline) were infused into the prelimbic region of the prefrontal cortex and dorsal hippocampus 40 minutes prior to testing on the win-shift task. The higher dose of estradiol facilitated working memory when infused into the prelimbic region, whereas lower doses of estradiol facilitated performance when infused into the hippocampus. Working memory performance was significantly impaired 24 hours after infusions of estradiol into the dorsal hippocampus relative to saline infusions. These data provide further evidence for the idea that estradiol can dose-dependently alter memory processes, and also suggest that the facilitation and impairment of working memory by estradiol is site- and time-specific. Chapter 2 sought to elucidate the role of long-term physiological levels of estradiol on the phosphorylation of cAMP response binding element (pCREB); a transcription factor related to cognitive processes. Ovariectomized rats were administered oil, high estradiol (5 μg estradiol benzoate) or low estradiol (0.3 μg estradiol benzoate) for 17 consecutive days. Neither dose of estradiol significantly altered the number of pCREB-positive cells in the dorsal CA1, CA3 or in the prelimbic region relative to control levels. There was however a time of day effect, with animals perfused 40 minutes after the last injection exhibiting more pCREB-positive cells than animals perfused 4 hours after the last injection. Future research is required to clarify the role that estradiol plays in the activation of CRJEB.

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