Correlation of Rodent Behavioural and Physiological Measures Following Different Combinations of Lifetime Stress

Abstract

<p>There are more than 200 classified forms of mental disorders, with depressive and anxiety disorders as the most prevalent in the world. These disorders represent a societal burden due to the impact on an individual's occupational, social, and personal commitments. Often these depressive and anxiety disorders develop following a stressful life event or series of stressful life events. The diagnosis of depressive and anxiety disorders rely solely on behavioural symptomology despite the fact that stress events also result in physiological symptoms. Furthermore, examination of behavioural and physiological changes in depressive and anxiety disorders is difficult because of the heterogeneity these disorders have in humans due to individual reactions to stress. This heterogeneity can be mitigated in rodent models of depressive and anxiety disorders using a consistent stress as the trigger. Thus, it was hypothesised that there is a connection between the stress-induced changes to behaviour and physiology that can be examined in a rat model. The connection between behaviours and physiological markers to stress can be used in further research to stratify depressive and anxiety disorder diagnosis in humans.</p> <p>A model combining early and recent life stress was designed to examine the longitudinal changes to behaviour in stress-resistant rats. At the end of the stress challenge post-mortem concentrations in stress hormones and cellular changes in adrenal glands, hippocampus, and hypothalamus were examined, based on the knowledge that stress often modifies these regions. The cumulative stress-induced behaviour and physiology changes were assessed for any associations. Given that stress impacts people differently depending on the circumstances, the model used a stress-resistant rat strain hypothesising that if stress-induced behaviour and physiology modifications occur in stress-resistant animals such changes will also occur in stresssusceptible strains.</p> <p>The combination of early and recent life stress did result in modification of behaviour and physiology. The observed stress-induced change in rat behaviour was determined as anxiety-like behaviour. Physiologically, there were changes to chronic stress hormones but not acute stress hormones. There were associations between the stress-induced cumulative behaviour and endpoint physiology modifications. Integrating stress-induced physiological symptoms with the behavioural symptoms of depressive and anxiety disorders can further the stratification of disorder diagnosis. Further research is required to expand the behavioural and physiological measures included to better define depressive- and anxiety-like behaviour in rats. This improvement can be used to further the stratification of depressive and anxiety disorder diagnosis, as well as to investigate novel pharmacological treatments for depressive and anxiety disorders in humans.</p>