Stress-responsiveness and the effect of antidepressants in juvenile animals

Abstract

Chronic stress is known to be a risk factor for the development of depression and anxiety, disorders which often begin during adolescence. Restraint stress is a commonly used stressor in adult rodents, however the effects of repeated restraint stress in juvenile mice have not been well characterised. Here, I have shown for the first time the behavioural and hormonal effects of repeated restraint stress in both adult and juvenile BALB/c and C57BL/6 mice, as well as the effect of repeated stress on gene expression of components of the HPA axis. Repeated daily restraint stress (2h/day for 3, 7 or 14 days) provoked a robust physiological response evident as increased corticosterone levels and decreased body weight after 14 days (↓8% adults, ↓12% juveniles) compared to controls. Increases in corticosterone after 3 days stress appeared to be greater in juvenile mice (2000% over baseline) than in adults (710% over baseline), in both strains of mice, suggestive of an increased sensitivity of the HPA axis. However, habituation of the stress-response was evident during longer durations of daily exposure to the stressor in both adult and juvenile mice. No changes in gene expression were observed following repeated stress. The behavioural changes seen in response to repeated restraint stress were complex. In juvenile mice, repeated restraint stress evoked an increase in exploratory behaviours in the elevated plus maze, a decrease in time spent immobile in the forced swim test and a decrease in sucrose preference. In adult mice fewer behavioural changes were seen. Interestingly BALB/c and C57BL/6 mice showed qualitatively similar response to 3 days repeated restraint stress despite previous reports that BALB/c mice are more stress sensitive. The behavioural changes we observed, as a result of prior stress exposure, may represent an adaptive stress-coping response or resilience. Both the hormonal and behavioural effects of stress were more pronounced in juvenile mice than in adults. This wider range of behavioural responses seen in juvenile mice might reflect a greater ability to engage in adaptive stress-coping strategies that likely have beneficial effects evident in future stress challenges.

Date of Award	2 Jun 2017
Original language	English
Awarding Institution	University of Bath
Supervisor	Sarah Bailey (Supervisor)