The influence of the duration of chronic unpredictable mild stress on the effectiveness of modeling depressive-like state in rats of different ages

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The aim of the study was to determine the optimal duration of chronic unpredictable mild stress (CUMS) exposure for the induction of depressive-like state (DLS) in rats of different ages. Male Wistar rats aged 6 weeks (young), 10 months (adult), and 20 months (old) were used in the experiment. The rats were divided into control and experimental groups that underwent 4-week and 7-week CUMS exposure, respectively. DLS was induced using the CUMS protocol, 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, and 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 beginning at 4 weeks following 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. Long-term exposure to chronic stress resulted in decrease in exploratory activity and an increase in anxiety levels in animals of all ages during the open field test. In the forced swimming test, the indications of behavioral despair, including the decline in latency to the first episode of immobility and an increase in 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.

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O. Nadeia

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

编辑信件的主要联系方式.
Email: olganadej@gmail.com
俄罗斯联邦, Saint-Petersburg

E. Prokopenko

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; Saint Petersburg State University

Email: olganadej@gmail.com
俄罗斯联邦, Saint-Petersburg; Saint-Petersburg

N. Agalakova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: olganadej@gmail.com
俄罗斯联邦, Saint-Petersburg

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2. Fig. 1. Changes in rat body weight during the DPS simulation using the CNS procedure. Control – control, CUMS – CNS. The mean values ​​± SE are presented (n = 10–14 for 4 weeks and 5–7 for 7 weeks). * p < 0.05, ** p < 0.01 compared to the corresponding control (two-way mixed ANOVA).

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3. Fig. 2. Ratio of adrenal gland weight to body weight of rats after the CNS procedure. Mean values ​​± SE are presented (n = 5 for 4 weeks and 5–7 for 7 weeks). * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the corresponding control (unpaired t-test).

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4. Fig. 3. Plasma corticosterone levels in rats of different ages after exposure to CNS. Mean values ​​± SE (n = 5) are presented. * p < 0.05, *** p < 0.001 compared to the corresponding control (Mann-Whitney test).

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5. Fig. 4. Results of the sucrose consumption test in rats from all age groups. Mean values ​​± SE are presented (n = 10 for 4 weeks and n = 5 for 7 weeks). * p < 0.05, ** p < 0.01 compared with the corresponding control (two-way mixed ANOVA).

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6. Fig. 5. Total immobility time and the delay period before the first episode of immobility in rats of different ages after 4 and 7 weeks of CNS. Mean values ​​± SE (n = 5–7) are presented. * p < 0.05, ** p < 0.01 compared with the corresponding control (unpaired t-test).

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