Chronic Subordinate Colony Housing (CSC) as a Model of Chronic Psychosocial Stress in Male Rats

Abstract

Chronic subordinate colony housing (CSC) is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH) responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min) despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

“…In agreement with previous reports, we showed that CSC mice exhibited reduced body weight gain which is a wellestablished physiological marker of chronic stress in both mice (Reber et al 2007;Reber and Neumann 2008;Singewald et al 2009) and rats (Berton et al 1998;Nyuyki et al 2012;Plaznik et al 1993;Stefanski et al 2001). A reduction in body weight gain was also observed in acutely defeated animals (Berton et al 1998).…”

Repeated psychosocial stress at night, but not day, affects the central molecular clock

“…However, since the decreased home-cage activity in the SDL group was restored to control levels on days 14 and 20, and, given that no differences in body weight gain were found between the SDL and SHC groups, our results are overall in accordance with our previous study showing that repeated SDD (night stress) has more profound effects than repeated SDL (day stress). In addition, we observed a reduced weight of thymus from SDD, but not SDL, mice that is a reliable indicator of chronic stress (Nyuyki et al, 2012). Taken together, we consider the SD paradigm valid also in the PER2::LUC mice.…”

Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

“…Unlike the spleen, the thymus often shrinks during stress and that shrinkage is directly proportional to the degree of stress and increase in plasma adrenocorticotropic hormone and corticosterone levels [33]. TNBS treatment resulted in significant decrease of thymus weight on days 3 and 6 (Fig.…”