Environmental enrichment as an intervention to prevent behavioral and neurobiological consequences of maternal separation in rodents: a scope review.

Neglectful care or disruption of the mother-infant relationship can alter the offspring's neurodevelopmental trajectory, inducing non-adaptative behaviors and negative neurobiological consequences. Environmental enrichment (EE), in turn, promotes the expression of animals' innate behaviors by providing cognitive, sensory, motor and social stimuli. Few studies have explored EE effects on animals with a previous history of early life stress, with maternal separation (MS) being the most frequently used paradigm. This scope review aimed to evaluate whether EE can prevent and/or reverse the deleterious effects induced by MS. Out of 182 retrieved papers, the 36 that were included assessed the outcomes of EE in maternally-separated animals. Behavioral endpoints included social, anxiety- and depression-like behaviors, memory and cognition, and alcohol intake. Neurobiological endpoints were HPA axis activity, neurogenesis, neuroplasticity, neuroinflammation, and resilience factors. We detected a great variation in MS and EE protocols, generating large variability of results. Nonetheless, robust evidence supports the beneficial EE effects in reversing or attenuating MS-induced learning and cognitive impairments. Moreover, EE shows promising effects in enhancing neurogenesis and the expression of resilience factors. Findings regarding affective and motivated behaviors are more variable, but they underline stronger benefits when EE is applied during the prepubertal and pubertal periods. The literature also suggests a sex dimorphism in EE responsiveness, with females being more resistant and requiring longer exposure to manifest the benefits. Overall, these findings reinforce the potential of EE as a non-pharmacological strategy to mitigate early life stress-induced alterations, while underscoring the need for standardized protocols and sex-specific investigations.