Sex differences in the neurogenic and behavioural effects of repeated estradiol administration in the adult rat

Estradiol affects neurogenesis in the hippocampus of adult female mammals, but relatively little is known about how estradiol affects cells in the male brain, or how repeated estradiol administration affects either sex. I show in this thesis that repeated estradiol affects cell production and neuron survival in the dentate gyrus of female, but not male rats. Specifically, estradiol administered to female rats increased cell proliferation, decreased the number of young neurons, and decreased the number of dying cells. This difference was not due to differential uptake of estradiol, as the administration of estradiol resulted in concentrations of estradiol in the serum, hippocampus, amygdala, and prefrontal cortex that were similar between males and females. The function served by the new neurons in the hippocampus remains controversial, but evidence suggests they may play a particularly important role in modulating performance in hippocampus-dependent tasks. I used a hippocampus-dependent task, contextual fear conditioning, to determine whether the effects of estradiol on different aspects of neurogenesis - or lack thereof - could be related to its effects on learning and memory. I found a consistent sex difference, with males spending more time freezing than females regardless of treatment. Furthermore, I found that repeated estradiol reduces the amount of time spent freezing in response to a novel context after training in females but not in males. Collectively my results suggest that repeated estradiol influences hippocampal structure and function in female but not male rats. Furthermore the production and survival of adult-generated neurons are regulated differently in males and females which has strong implications for any potentially therapeutic manipulations of these cells.Medicine, Faculty ofGraduat