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The effects of prenatal ethanol exposure on anterior pituitary sensitivity and elevated plus maze behaviour following CRH stimulation

University of British Columbia

Previous studies have shown that following prenatal ethanol exposure, rats exhibit hormonal hyperresponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis and behavioural hyperresponsiveness to stressful stimuli. The studies conducted in this thesis investigated the effects of prenatal ethanol exposure on HPA axis function and on behaviour in the elevated plus maze. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) treatment groups were tested in adulthood in all studies. Two major studies were conducted. The first study investigated the hypothesis that the HPA hyperresponsiveness observed in animals prenatally exposed to ethanol is due at least in part to an increased responsiveness of the anterior pituitary to CRH stimulation. Following dexamethasone suppression, CRH-induced plasma ACTH and CORT were compared between animals from E, PF and C treatment groups. Higher doses of CRH resulted in higher and more prolonged ACTH and CORT responses in both males and females. Overall, females demonstrated greater increases in plasma ACTH levels in response to exogenous CRH compared to males. Importantly, E females but not E males showed increased plasma ACTH responses to CRH as compared to their PF and C counterparts during the trough but not during the peak of the HPA circadian rhythm. The results of this study suggest that E animals exhibit increased anterior pituitary responsiveness to CRH stimulation at least during the trough of the HPA circadian rhythm. Furthermore, females may be more vulnerable to the effects of prenatal ethanol exposure compared to males. The second study investigated the hypothesis that behavioural hyperresponsiveness observed in animals prenatally exposed to ethanol is mediated by an increased sensitivity of the central nervous system to CRH. The anxiogenic effects of low or high doses of CRH administered centrally with or without D-Phe-CRH (a CRH antagonist) on elevated plus maze behaviour were compared between animals from E, PF and C treatment groups. Intracerebroventricular administration of CRH increased fear-related behaviour as indicated by decreased time on and entries into open arms, and increased time on closed arms; and decreased exploration and motor activity as indicated by decreased entries into closed arms, total entries and total rears. D-Phe-CRH reversed the effects of CRH on some but not all of the behavioural measures. Overall, females required higher doses of CRH to elicit behavioural effects which are the same levels as seen in males, suggesting that females are less sensitive to the behavioural effects of CRH than males. Importantly, E males showed increased fear-related behaviour and decreased exploration and motor activity in the elevated plus maze compared to PF and C males. Furthermore, following administration of CRH, E animals showed increased fear-related behaviour and decreased exploration and motor activity compared to PF and C animals. The results of this study suggest that E animals exhibit an increased responsiveness to the behavioural effects of centrally administered CRH.

Thesis/Dissertation

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2009-03-24

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http://hdl.handle.net/2429/6367

Anatomy, Cell Biology and Physiology

University of British Columbia

UBCV

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