Mice selected for high or low stress reactivity: a proposed model for affective disorders

Alterations of the stress hormone systems, in particular dysfunctions of the hypothalamic-pituitary-adrenal (HPA) axis, play a major role in the development of depression and comorbid anxiety. Therefore, we set out generating a new animal model comprising these core symptoms in order to unravel parameters underlying increased stress reactivity.

Starting from a population of outbred mice, two breeding lines were established according to the outcome of a ‘stress reactivity test’ (SRT) consisting of a 15 minute restraint and blood samplings immediately before and after exposure to the stressor. Mice showing a very high or very low secretion of corticosterone in the SRT were selected for the ‘high reactivity’ (HR) and the ‘low reactivity’ (LR) breeding line, respectively. Additionally, a third breeding line was established consisting of animals with an ‘intermediate reactivity’ (IR).

Already in the first generation, significant differences in the reactivity of the HPA axis between HR, IR and LR mice were confirmed. Tests investigating anxiety-related and depression-like behaviour as well as neuroendocrine alterations in these animals were also performed and will help to link genetic differences between the lines with trait specific phenomena.

Thus, the generated HR/IR/LR mouse lines can be a valuable model to elucidate genetic, neuroendocrine and behavioural parameters associated with increased stress reactivity and thereby improve our understanding of affective disorders.