Parental care shapes anxiety-like behavior, oxytocin, social interaction, and ethanol sensitivity in adolescent C57BL/6J mice

Abstract

Rationale: Parenting conditions significantly affect neurodevelopment. Previous preclinical studies show that adolescents reared by a single mother (SM) exhibit an anxiety-prone phenotype, greater activation of anxietyrelatedbrain regions, enhanced sensitivity to ethanol-induced anxiolysis, and higher ethanol intake compared to biparentally reared (BP) peers. However, it remains unclear whether this phenotype is accompanied by alterationsin the oxytocinergic system and associated changes in social behavior during adolescence.Objectives: To analyze whether SM rearing is associated with alterations in the oxytocinergic system, social behavior, and ethanol-related behavioral responses.Methods: Adolescent C57BL/6J mice raised in SM or BP conditions were assessed for a) anxiety-like behavior and ethanol-induced anxiolysis in the elevated plus maze (EPM), b) neural oxytocin (OT) immunofluorescence in hypothalamic nuclei, and c) social behavior and ethanol-induced changes in social interaction.Results: Ethanol increased time spent in the open arms of the EPM, indicating an anxiolytic-like effect. SM adolescents displayed a more anxiety-like behavioral profile, characterized by increased risk-assessment behavior. BP mice showed higher OT fluorescence intensity in the paraventricular hypothalamic nuclei and greater social interaction compared to SM counterparts. Moderate ethanol doses reduced social interaction independently of rearing condition.Conclusions: Early parenting conditions shape adolescent neurobehavioral outcomes. SM rearing was associated with heightened anxiety-like behavior, reduced hypothalamic OT immunofluorescence, and diminished social interaction. Ethanol exerted domain-specific effects, promoting anxiolysis while decreasing social behavior. These findings suggest that early family structure influences oxytocin-related circuits involved in socio-emotional regulation and may contribute to vulnerability to anxiety-related traits during adolescence.