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Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial ability improves, which can be better than non-stressed controls (CON). The WO period is often the same duration as the

Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial ability improves, which can be better than non-stressed controls (CON). The WO period is often the same duration as the chronic stress paradigm. Given the potential benefit of a post-stress WO period on cognition, it is important to investigate whether this potential benefit of a post-stress WO period has long-lasting effects. In this project, chronic restraint (6hr/d/21d) in Sprague-Dawley rats was used, as it is the minimum duration necessary to observe spatial memory deficits. Two durations of post-stress WO were used following the end of chronic restraint, 3 weeks (STR-WO3) and 6 weeks (STR-WO6). Immediately after chronic stress (STR-IMM) or the WO periods, rats were tested on various cognitive tests. We corroborated past studies that chronic stress impaired spatial memory (STR-IMM vs CON). Interestingly, STR-WO3 and STR-WO6 failed to demonstrate improved spatial memory on a radial arm water maze task, performing similarly as STR-IMM. Performance outcomes were unlikely from differences in anxiety or motivation because rats from all conditions performed similarly on an open field task and on a simple object recognition paradigm, respectively. However, performance on object placement was unusual in that very few rats explored, suggesting some degree of anxiety or fear in all groups. One possible interpretation of the unusual results of the 3 week washout group may be attributed to the different spatial memory tasks used across studies or external factors from the study. Further exploration of these other factors led to the conclusion that they did not play a role and the STR-WO3 RAWM data were anomalous to other studies. This suggests that a washout period following chronic stress may not be fully understood.
ContributorsFlegenheimer, Aaron Embden (Author) / Conrad, Cheryl (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

ContributorsArroyo, Mariana (Author) / Bimonte-Nelson, Heather (Thesis director) / Jurutka, Peter (Committee member) / School of International Letters and Cultures (Contributor) / School of Social and Behavioral Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit impaired cognition and increased depressive and anxiety-like behavior following chronic

Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit impaired cognition and increased depressive and anxiety-like behavior following chronic stress. The primary goal of this dissertation was to reveal novel elements contributing to female susceptibility to stress-induced depressive-like presentations and possible factors that may counteract such outcomes. In chapter 2, novel stress paradigms were investigated to determine whether more robust stressors would lead to spatial memory deficits and elevated anxiety in young adult female and male rats. Results demonstrated that chronic stress impaired spatial memory in males, while the robust stressors failed to impair spatial memory in females. Chapter 3 revealed that both females and males in chapter 2 showed BLA dendritic hypertrophy days following the stressor without hippocampal alterations, with the latter likely due to the passage of time allowing for restructuring. Consequently, chapters 4 through 6 were conducted to investigate whether females would show chronic stress effects at middle-age in ovariectomized (OVX) females because menopause is a period of high vulnerability to cognitive and depressive-like effects. Chapter 4 investigated whether the stress hormone, corticosterone, would impair spatial working memory and increase the depressive-like profile of OVX, middle-aged female rats, which was confirmed using the radial arm water maze (RAWM), sucrose preference (SP), forced swim test (FST), and elevated plus maze (EPM). Chapter 5 investigated if estradiol (E2) may prevent the negative valence outcomes induced by OVX in middle-aged female rats. However, E2 showed antidepressant properties during FST, but failed to do so in other behavioral tasks. Chapter 6 further explored E2’s role in mitigating corticosterone-induced effects on cognition and mood in middle-aged female and male rats, with more pronounced antidepressant effects in females. Notably, this chapter unveiled a novel correlation between spatial memory and anxiety-like behavior in corticosterone-treated female rats. Collectively, these studies delineate a corticosterone-based model of depression in female rodents and introduce a novel approach for analyzing variables across multiple behavioral domains.
ContributorsPeay, Dylan (Author) / Conrad, Cheryl D (Thesis advisor) / Bimonte-Nelson, Heather (Committee member) / Verpeut, Jessica (Committee member) / Huynh, Thu (Committee member) / Arizona State University (Publisher)
Created2023