Florey Department of Neuroscience and Mental Health - Theses
Permanent URI for this collection
Search Results
1 - 1 of 1
-
ItemEarly life stress and the extinction of conditioned fear in the developing rat( 2021)Early life stress is a known antecedent to anxiety- and fear-related disorders. It may disrupt the ability to regulate fear and act to trigger the development of an anxiety- or fear-related disorder. Hence, in this thesis, I examined the link between early life stress and fear regulation across development. To do this, I used Pavlovian fear extinction as a model of fear regulation to assess the effects of infancy and peri-adolescent stress in rats. In Chapter 2, I examined whether a chronic infancy stressor altered fear extinction in juvenile rats. This series of experiments utilized the limited bedding and nesting model of chronic infancy stress. I found that chronic infancy stress resulted in the precocious emergence of relapse-prone fear in male juvenile rats. However, chronic infancy stress had little effect on extinction behavior in female juvenile rats, as they exhibited relapse-prone fear regardless of stress condition. In Chapter 3, I investigated whether chronic peri-adolescent stress altered fear extinction in adolescence and adulthood. This series of experiments utilized social isolation as a model of chronic peri-adolescent stress. Peri-adolescent stress had a sex-specific effect on fear extinction. In males, peri-adolescent stress resulted in impairments in extinction recall in adolescent and adult male rats. However, in females, peri-adolescent stress had no effect on fear extinction behavior. In Chapter 4, I explored the interplay between peri-adolescent stress and physical activity on fear extinction in adolescence. Peri-adolescent stress, as modelled by social isolation, impaired extinction recall in male adolescents, but this effect was prevented by increased physical activity. Extinction recall in female adolescents was again unaffected by peri-adolescent stress. Surprisingly, increased physical activity was disruptive to extinction recall in peri-adolescent stressed females. Pharmacological suppression of cellular proliferation in peri-adolescent stressed adolescents blocked the effect of physical activity on extinction recall in both sexes. This suggests that peri-adolescent born cells mediate the interplay between peri-adolescent stress and physical activity effects on extinction behavior. Together, these findings highlight sex-specific outcomes of peri-adolescent stress and physical activity on adolescent brain and behavior. In the final Chapter, I propose the Variable Speed Stress model to interpret the effects of stress in infancy and peri-adolescence. Further, I outline potential reasons for the sex effects and possible avenues for future research. Overall, the findings in this thesis contribute to our understanding of how early life stress affects fear extinction throughout development. It suggests that after early life adversity, stress-induced changes to extinction learning development in males may contribute to a reduction in treatment efficacy for exposure-based anxiety disorder therapies.