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• W186352477 abstract "In humans, chronic stress is regarded as a major risk factor for the development of a variety of affective and somatic disorders, among them anxiety, depression, post traumatic stress disorder, inflammatory bowel disorders, chronic fatigue syndrome, chronic pelvic pain and fibromyalgia. In order to determine the exact underlying mechanisms and also to find pharmacological treatment, a large number of models have been used to induce chronic stress in rodents. However, conventional rodent models of chronic stress including restraint, forced swim and inescapable footshock for example; are unnaturalistic, of time-limited exposure and do not consider the etiology of human stress-associated disorders, where the main source of stress stimuli is of social origin. Consequently, a greater amount of attention has been focused upon developing animal models that utilize more naturalistic experimental paradigms to model stress that is ethologically relevant to the model organism.Accordingly, a clinically relevant animal model of chronic psychosocial stress (CPS); chronic subordinate colony housing (CSC) has recently been established and extensively characterized in our group. It consists of housing 4 experimental adult male mice together with a slightly larger and more dominant conspecific over 19 consecutive days, exchanging the dominant male weekly in order to prevent habituation. This consequently results in a reduced body weight gain, thymus atrophy and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Of particular importance to this thesis is the unchanged morning basal plasma corticosterone, but a reduced adrenal response to corticotrophin (ACTH) in vitro. With respect to the growing use of genetic mouse models in general, and the need to study in vivo responsiveness of the HPA axis especially with regards to the CSC model, one of the objectives of this thesis was to devise a technique by which blood samples can be repeatedly drawn from conscious mice under stress-free conditions. Therefore, a simplified jugular vein catheterization technique was established and validated. This thesis showed that repeated blood sampling is possible in mice 24 h after surgery, and that corticosterone concentrations in repeated 100-μl venous blood samples were similar to trunk blood, both collected under basal conditions and at identical time points (5, 15 and 60 min) after stressor exposure. Further, anxiety-related behavior, as assessed on the elevated plus-maze 3 to 4 days after surgery did not differ between catheterized and non-catheterized mice. In parallel, as the main objective of this thesis, the CSC model was extended to male Wistar rats in order to i), investigate if the reported behavioral, physiological, immunological and neuroendocrine changes accompanying CSC in mice are species specific and ii), characterize in substantial detail, in vivo neuroendocrine changes following CSC which till moment have not been possible in mice, e.g plasma ACTH. Consistent with the results in mice, 19 days of CSC exposure in rats resulted in a decreased body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in depressive-like behaviour or social preference were observed. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor, despite displaying similar basal levels and similar basal and stressor-induced plasma corticotrophin (ACTH) levels in samples repeatedly collected via a chronically implanted jugular vein catheter. In contrast to CSC mice, anxiety-related behaviour and absolute adrenal weights remained unchanged in CSC rats. In this regard, risk factors that could influence the susceptibility to CSC were further investigated.There is a plethora of literature addressing the involvement of adverse early life events and genetic predisposition as risk factors in the vulnerability to chronic stress in adulthood. Therefore, this thesis made use the high (HAB) and low (LAB) anxiety-related behaviour animal models of anxiety, as well as prenatally stressed male Wistar offspring. Specifically, HAB and LAB rats also show robust differences in depressive-like behaviour, neurobiochemical responses and neurogenetic constitution. It was therefore revealed that after 19 days of CSC, prenatally stressed rats gained less body weight and had a higher histological damage score. No changes in adrenal weight, basal plasma corticosterone levels, as well as anxiety-related behaviour were observed. The present study could not reveal any difference in HAB and LAB rats in their response to CSC in adulthood, but both lines were independently affected by CSC. Anxiety-related behaviour tested in the light-dark box after CSC was not altered, thus confirming the results in non-selected rats. CSC induced a decrease in body weight gain and thymus mass, but no changes in adrenal mass, basal plasma corticosterone and colonic morphology in both HAB and LAB rats. In a nutshell, this thesis demonstrates that chronic jugular vein catheterization and stress-free repeated blood sampling is possible in conscious mice using our relatively simple catheter and sampling technique. It also establishes the CSC paradigm as an adequate model of CPS in male rats. Consistent to mice data, our data from repeated blood sampling supports the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed animal to adequately respond to novel challenges. We further reveal that early life stress increases the vulnerability to chronic psychosocial stressors during adulthood, with respect to inflammatory disorders like colitis and that genetic predisposition, in terms of genetically determined differences in innate anxiety-related behaviour do not shape susceptibility to chronic psychosocial stressors during adulthood." @default.
• W186352477 created "2016-06-24" @default.
• W186352477 creator A5043527172 @default.
• W186352477 date "2013-02-20" @default.
• W186352477 modified "2023-09-27" @default.
• W186352477 title "Consequences of chronic psychosocial stress in male wistar rats" @default.
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