The Influence of the Duration of Chronic Unpredictable Mild Stress on the Effectiveness of Modeling Depressive-Like State in Rats of Different Ages

The aim of the study was to determine the optimal durationof chronic unpredictable mild stress (CUMS) exposure for the formationof depressive-like state (DLS) in rats of different ages. Male Wistar ratsaged 6 weeks (named young), 10 months (adult), and 20 months (old)were divided into control and experimental groups. DLS was inducedusing the CUMS procedure, for which the animals were subjected toalternating short and long-term stress stimuli for 4 or 7 weeks.The hedonic state of the rats was assessed by their preferencesfor sucrose, while the development of DLS was evaluated using open fieldand forced swim tests, as well as by corticosterone levels in bloodplasma. In rats from all age groups, the reduction in sucrose intakewas observed starting from 4th week after the exposure to chronicstress. However, all individuals in the CUMS groups were classifiedas having anhedonia-like symptoms after 7 weeks of stress exposureonly. Longer exposure to chronic stress resulted in decreased exploratoryactivity and an increased anxiety in animals of all ages in theopen field test. In the forced swimming test, the signs of behavioraldespair including the decline in latency to the first episode ofimmobility and an increase in the total duration of immobility werealso more pronounced in rats exposed to stress for 7 weeks. Additionally,young rats that underwent CUMS protocol demonstrated more prominent behavioralabnormalities compared to adult and older individuals. 7-weeks ofCUMS exposure led to significant increase in corticosterone levels,indicative of DLS, in all rats. Therefore, the findings from all testssuggest that a longer CUMS protocol is required for the developmentof depression-like behavior in male Wistar rats, and younger individualsare more vulnerable to the effects of chronic stress.