Investigating the role of environmental enrichment initiated in adolescence against the detrimental effects of chronic unpredictable stress in adulthood: Sex-specific differences in behavioral and neuroendocrinological findings

Environmental Enrichment (EE) improves cognitive function and enhances brain plasticity, while chronic stress increases emotionality, impairs learning and memory, and has adverse effects on brain anatomy and biochem-istry. We explored the beneficial role of environmental enrichment initiated in adolescence against the negative outcomes of Chronic Unpredictable Stress (CUS) during adulthood on emotional behavior, cognitive function, as well as somatic and neuroendocrine markers in both sexes. Adolescent Wistar rats housed either in enriched or standard housing conditions for 10 weeks. On postnatal day 66, a subgroup from each housing condition was daily exposed to a 4-week stress protocol. Following stress, adult rats underwent behavioral testing to evaluate anxiety, exploration/locomotor activity, depressive-like behavior and spatial learning/memory. Upon comple-tion of behavioral testing, animals were exposed to a 10-m stressful event to test the neuroendocrine response to acute stress. CUS decreased body weight gain and increased adrenal weight. Some stress-induced behavioral adverse effects were sex-specific since learning impairments were limited to males while depressive-like behavior to females. EE housing protected against CUS-related behavioral deficits and body weight loss. Exposure to CUS affected the neuroendocrine response of males to acute stress as revealed by the increased corticosterone levels. Our findings highlight the significant role of EE in adolescence as a protective factor against the negative effects of stress and underline the importance of inclusion of both sexes in animal studies.