Gestational environmental enrichment modulates neurophysiological and behavioral outcomes in adolescent rats after early-life stress: Sex differences in emotional and social behavior

Abstract

The perinatal environment critically shapes neurodevelopmental trajectories. Early life stress (ELS), particularly when associated with disrupted maternal care, has been linked to long-lasting neurobiological and behavioral alterations. This study explored the potential of gestational environmental enrichment (EE) to modulate these effects in a rodent model. Pregnant Wistar rats were housed under either EE or standard conditions (SC); offspring were subsequently exposed to stress paradigms, including maternal separation (MS), intruder male (IM) or no stress (NS) during lactation. In adolescence, males and females were evaluated for anxiety-like and social behaviors using elevated plus maze, open field, and social preference tests. A composite Z-score was calculated to provide a comprehensive measure of anxiety-related behaviors by integrating the parameters from the elevated plus maze and open field tests. Additionally, neuronal activity in regions associated with emotional and social regulation was analyzed. Our findings revealed significant sex-dependent differences in behavioral outcomes. Females exhibited reduced anxiety-like behaviors and greater exploratory activity than males, regardless of ELS exposure or gestational housing. Gestational EE mitigated anxiety-like behaviors, as indicated by reduced Z-scores and modulated social interaction patterns in both sexes, although specific effects varied according to stress condition. At the neural level, EE enhanced ΔFosB expression in the basolateral amygdala of MS offspring, while ELS reduced hippocampal ΔFosB, particularly in the dentate gyrus and CA2 regions. Moreover, sex-dependent patterns of ΔFosB activity emerged across amygdalar and hippocampal circuits, aligning with the behavioral differences observed. These results suggest that EE buffers ELS effects by differentially recruiting amygdalo-hippocampal circuits, highlighting sex-specific vulnerability and resilience mechanisms relevant to neurodevelopment.