Sex‐Dependent Neurochemical Encoding of Acute Social Experience in Adult CD1 Mice

ABSTRACT

Acute social interaction rapidly engages physiological and neurochemical systems, yet the extent to which these responses differ between sexes remains incompletely understood. Here, we investigated behavioural, endocrine and region‐specific neurochemical responses to a brief social challenge using the social interaction test in adult male and female CD1 mice. Behavioural performance was comparable between sexes, with similar levels of social interaction and locomotor activity. In contrast, endocrine measures revealed a robust stress response, as corticosterone markedly increased after social challenge. Estradiol and progesterone levels also increased following the social challenge, whereas testosterone exhibited the expected sexual dimorphism. Neurochemical profiling revealed widespread and region‐dependent effects. The brainstem showed manipulation‐driven increases in glutamatergic and catecholaminergic markers across sexes. In the striatum, social interaction preferentially enhanced glutamatergic metabolites in males, whereas females displayed stronger monoaminergic signatures. The hippocampus exhibited the most pronounced sex‐dependent modulation, involving amino‐acid precursors, catecholaminergic turnover indices, noradrenergic metabolites and kynurenine‐pathway ratios. By contrast, neurochemical organisation in the prefrontal cortex was predominantly shaped by baseline sexual dimorphism rather than acute social exposure. Correlation analyses between plasma hormones and regional neurochemical markers revealed limited and inconsistent associations, suggesting a relative dissociation between endocrine and neurochemical responses to the social challenge. Together, these findings demonstrate that acute social interaction induces broad endocrine and neurochemical adaptations while revealing distinct, region‐specific sex signatures in neurochemical regulation.

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