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

Τhe neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review

“…Similarly, Smith and colleagues found that exposure of adolescent male and female rats (PND33-60) to CUMS (4 weeks) resulted in passive coping behavior in FST and decreased exploration in OFT in adulthood, in females only, while housing in EE, initiated in adolescence and prior to CUMS, attenuated passive coping behavior, but did not affect exploration (Smith et al, 2018). Likewise, our group recently reported that adult CUS induced depression-like behavior, as indicated by increased immobility time in FST, only in females, an effect that was prevented by EE housing (Dandi et al, 2022). Concerning the sex-related effect of CUMS, it has been previously reported that females are especially susceptible to the long-term negative effects of CUMS on emotional behavior.…”

“…Most of these studies agree that EE housing initiated before, during or post CUMS restores cognitive deficits and counterbalances depressive and anxiety-related behavior caused by stress exposure (Cordner & Tamashiro, 2016;Dandi et al, 2022;Gu et al, 2021;Ilin & Richter-Levin, 2009;Liu et al, 2017;Seo et al, 2021;Shen et al, 2019;Shtoots et al, 2018;Xu et al, 2022). Additionally, it attenuates CUMSassociated increases in basal levels of stress hormones and compensates the reduced expression of synaptic plasticity markers, as well as the decreased neurogenesis and dendritic atrophy (Branchi et al, 2013;Dandi et al, 2022;Liu et al, 2017;Seong et al, 2018;Smith et al, 2018). In addition, there are studies investigating the role of inflammatory factors in the brain of stressed animals, since inflammatory changes have been linked to depression (Beurel et al, 2020).…”

“…In a recent study investigating the interaction between EE initiated in adolescence and adult CUMS, stress-related spatial learning impairments were limited to male rats. Interestingly, living in an enriched environment protected against these deficits (Dandi et al, 2022).…”

“…In addition, EE concurrently with CUMS condition reversed the decreases in peak adrenocortical responsiveness caused by adolescent CUMS in adult females (Smith et al, 2018). Interestingly, stress-induced corticosterone elevations in response to an acute stressor have been detected only in male rats previously exposed to CUMS and EE initiated in adolescence increased corticosterone levels in non-stressed males and CUMS females (Dandi et al, 2022) (see Table 3).…”

“…In fact, according to our literature search both sexes have been included only in two studies and their results indicate sex-related differences. Specifically, stress-related spatial learning impairments were limited to males (Dandi et al, 2022), while CUMS induced depression and anxietylike behavior only in female rats (Smith et al, 2018). The behavioral and neurobiological sex-related differences observed in models of anxiety and depression, raise the question whether the outcome of many studies which employed only males, could be replicated in females (Kokras & Dalla, 2014).…”