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.
Highlights
In humans, chronic stress has been repeatedly shown to be a risk factor for the development of several affective and somatic disorders
In contrast to the reduced adrenal in vitro ACTH responsiveness, we recently showed an increased in vivo plasma corticosterone response to an acute heterotypic stressor, namely exposure to an elevated platform, in chronic subordinate colony housing (CSC) compared with singlehoused control (SHC) mice [18]
Statistical analysis revealed that CSC compared with both SHC and GHC rats showed a decrease in body weight gain (F2,97 = 20.09; p,0.001; p,0.001 vs. both SHC and GHC; Figure 3A) and absolute thymus weight (F2,97 = 3.44; p = 0.036; p = 0.050 vs. SHC; p = 0.016 vs. GHC; Figure 3B), whereas absolute adrenal weight (F2,97 = 2.09; p = 0.129; Figure 3C) and basal plasma corticosterone (F2,97 = 0.28; p = 0.756; Figure 3D) in trunk blood were not different between the groups
Summary
Chronic stress has been repeatedly shown to be a risk factor for the development of several affective and somatic disorders (for review see [1,2]). There is a large body of evidence from rodent studies indicating a link between chronic or repeated stress and emotional, social and physiological, in particular immunological, dysfunctions [3,4,5,6,7] Despite this knowledge and substantial research efforts in the last decades, the aetiology of stress-based disorders remains poorly understood. CSC affects adrenal functionality resulting in unaffected basal morning, but decreased basal evening, plasma corticosterone levels [12], and a reduced adrenal in vitro ACTH responsiveness [12,18] These findings, at least at the first glance, suggest the development of adrenal insufficiency and, seem to be in line with the negative immunological and behavioural consequences of CSC in mice
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