Validating inactivity in the home-cage as a depression-like state indicator in mice

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Non-human animals (hereafter animals) can become strangely inactive in their home pens, being motionless (although awake) and not interacting with their environment. The affective states associated with this waking inactivity are, however, still not well understood. Compellingly, reduced activity and lack of engagement with the environment is one phenomenon supporting clinical depression diagnosis in humans. Moreover, the aetiology of human depression emphasizes aversive life events and chronic stress as common triggers of the disorder, and animals showing waking inactivity have often experienced an array of stressors, such as living in socially and/or spatially restricted environments. We therefore propose that,in animals, specific forms of waking inactivity characterised by being immobile with eyes open represent a marker of depression-like conditions.This project builds upon our research that has already delineated in mice Mus musculus a specific form of waking inactivity [being awake but motionless within the home cage], triggered by relatively barren lab cages and associated with a key depression-like symptom of the human illness: the tendency to give up when faced with challenge. Our goal is to further test the hypothesis that waking inactivity is a spontaneous depression-like symptom in mice, which would be an easily measured home-cage indicator of animal welfare that could be translated across species. To achieve this goal, we will adopt a translational 'from humans to animals' approach, using depressed people as a 'model' for inactive mice. As such, potential markers of animal depression-like conditions are expected to co-vary with a range of symptoms in animals similar to those described in human depression. Moreover, for an animal condition to be deemed homologous to a human illness, the processes by which both animal and humans fall into, and are released from, this state must share similarities. If waking inactivity reflects depression-like states in mice, its risk and curative factors should thus be similar to those of the human disease. Our investigations will thus broadly target shared aetiology [is waking inactivity triggered by a combination of risk factors triggering clinical depression in humans?], symptomatic similarities [does waking inactivity co-vary with a range of symptoms similar to those of clinical depression in humans?], and common curative factors [is waking inactivity alleviated by treatments clinically efficient in humans?]. Cognitive symptoms are a frequent part of depression in humans. A quick and easy cognitive measure of depression-like states is however needed in animals, and we will thus first validate such a measure of in mice, and then use this later to assess the symptomatic similarities between waking inactivity in mice and depression in humans.If confirmed, our results will validate in-cage waking inactivity as a marker of a depression-like condition in mice. This has clear implications for animal welfare, as validated methods of identifying states of mental suffering are first required if we are to detect welfare problems in situ, assess the effectiveness of refinements, and maximise the welfare of lab animals. The ability to detect depression-like states also has crucial implications from a research perspective, since mice in negative affective states may for instance represent improved models of human depression, while potentially invalidating research where stress and depression are not of interest. A new, non-invasive tool to measure affective states will thus be of interest to animal welfare scientists, neuroscientists & psychopharmacologists interested in the assessment of animal affect; biomedical scientists whose research may be impacted by spontaneous occurrence of depression-like states in their subject animals; and laboratory managers & scientists seeking to improve welfare of their research animals.