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 duration of chronic unpredictable mild stress (CUMS) exposure for the formation of depressive-like state (DLS) in rats of different ages. Male Wistar rats aged 6 weeks (named young), 10 months (adult), and 20 months (old) were divided into control and experimental groups. DLS was induced using the CUMS procedure, for which the animals were subjected to alternating short and long-term stress stimuli for 4 or 7 weeks. The hedonic state of the rats was assessed by their preferences for sucrose, while the development of DLS was evaluated using open field and forced swim tests, as well as by corticosterone levels in blood plasma. In rats from all age groups, the reduction in sucrose intake was observed starting from 4th week after the exposure to chronic stress. However, all individuals in the CUMS groups were classified as having anhedonia-like symptoms after 7 weeks of stress exposure only. Longer exposure to chronic stress resulted in decreased exploratory activity and an increased anxiety in animals of all ages in the open field test. In the forced swimming test, the signs of behavioral despair including the decline in latency to the first episode of immobility and an increase in the total duration of immobility were also more pronounced in rats exposed to stress for 7 weeks. Additionally, young rats that underwent CUMS protocol demonstrated more prominent behavioral abnormalities compared to adult and older individuals. 7-weeks of CUMS exposure led to significant increase in corticosterone levels, indicative of DLS, in all rats. Therefore, the findings from all tests suggest that a longer CUMS protocol is required for the development of depression-like behavior in male Wistar rats, and younger individuals are more vulnerable to the effects of chronic stress.