International Journal of Comparative Psychology

Psychosocial stress exposure during sensitive periods of development affects brain circuits involved in emotional regulation and contributes to the emergence of mood disorders as well as alterations in peripheral organ function. Most experimental studies have used post-weaning social isolation (SI) spanning the entire adolescent period to model early-life adversity. However, adolescence comprises heterogeneous developmental phases, marked by region-specific brain maturation and dynamic endocrine changes. Exposure to adverse environments during these distinct windows may therefore produce divergent behavioral and physiological outcomes. Yet, the role of developmental timing in determining the susceptibility of peripheral organs to stress remains poorly understood. Here, we assessed the immediate effects of a 10-day acute SI protocol, starting in mid-adolescence (postnatal day [PND] 35) in male NMRI mice, a stage where adolescence overlaps with puberty. We evaluated a on broad range of behavioral outcomes and on peripheral physiology, including renal and hepatic function through blood biochemistry analysis, in order to determine how stress exposure during a specific developmental window impacts both central and peripheral physiological processes.  Our results revealed that mice housed in SI exhibited a hyperactivity phenotype and increased anxiety-like and depressive-like states, while cognitive function remained intact. At the peripheral level, SI induced early signs of hepatic stress under basal conditions, reflected by elevated plasma alanine aminotransferase (ALT) levels, without evidence of renal injury. Together, these results highlight the critical importance of developmental timing in shaping stress-related behavioral and peripheral outcomes and suggest that mid-adolescence constitutes a window of heightened vulnerability.