Physical activity as a promoter of stress resilience: An analysis of behavioral effects and brain connectivity with cytochrome c-oxidase activity in adult male Wistar rats

Physical activity (PA) is very beneficial for physical and mental health. This study aims to examine the resilience-inducting effect of PA in adult male Wistar rats exposed to unpredictable chronic mild stress (UCMS). Furthermore, we analyzed the influence of PA on behavioral tasks and functional brain connectivity with cytochrome c oxidase technique. The cytochrome c oxidase (CCO) is a mitochondrial enzyme involved in oxidative phosphorylation and ATP generation. For this analysis, we included five groups: Basal (n = 10, to determine the basal level of brain activity), Behav (n = 15, subjected exclusively to behavioral tests), PA (n = 10, exposed to physical activity), UCMS (n = 15, subjected to a stress protocol) and PA + UCMS (n = 15, exposed to PA prior to stress). The UCMS protocol consisted of randomly presenting several different stressors over four consecutive weeks. We evaluated several behaviors of the Behav, UCMS, and PA + UCMS groups. This assessment includes the hedonic responses using the sucrose consumption task, unconditioned anxiety with the zero maze, and coping strategies assessed with the cat odor test. The UCMS group showed an anhedonia profile and increased anxiety compared with the other groups. Although in the exposure to cat odor test, the PA + UCMS remained for the same time in the cat odor compartment as the other groups, it did not approach the odor, showing that it detected the risk. This response is more adaptive than the responses of the UCMS and Behav groups. An exploratory analysis of the cerebral connections showed an increase in CCO activity in the UCMS group compared to the other groups. This overactivity was reduced in dorsal Cornu Ammonis 3(dCA3) by prior PA. In this region, PA + UCMS showed similar activity as the groups not subjected to chronic stress. Therefore, PA can prevent the harmful effects of chronic stress on dCA3. [Display omitted] •Physical activity promotes behavioral resilience.•Unpredictable chronic mild stress induces elevated anxiety and anhedonic responses in male rats.•Physical activity modifies the brain's organization in adult rats.