A "personality test" for rats reveals subtle but distinct effects of sex and early life inflammation on brain and behavior.

Abstract

Early life inflammation has long been associated with increased risk of later neuropsychiatric developmental disorder (NDD) diagnosis in humans. However, despite converging lines of evidence implicating the immune system in NDD etiology combined with reported sex differences in NDD diagnosis rates and the increasingly appreciated role of traditionally immune-associated factors in the sexual differentiation of the brain, a direct link connecting these three processes remains elusive. Here, we sought to characterize the enduring effects of early life inflammation in male and female rats exposed to the viral mimetic polyinosinic:polycytidylic acid (poly(I:C), 5 mg/kg) on Postnatal Day 8 (P8) and P10, a sensitive period we previously identified. We assessed a variety of behaviors-from juvenile social play to adult reward-guided decision making-and recorded from single neurons in nucleus accumbens as rats performed a task commonly used to assess cognitive control. All assessments were performed in the same animals allowing for exploratory factor analysis, which identified five factors that together reveal novel connections between behavioral measures across the lifespan and neural activity patterns. Collectively, this work suggests that viral-mediated inflammation at this developmental timepoint is not a robust risk factor for an NDD-like phenotype in rats. However, factor analysis revealed that sex and early life inflammation shifted two distinct modalities of rat "personality," highlighting the utility of combining modern neuroscience approaches with the study of complex, naturalistic behaviors. Future work should directly test these putative factor associations to determine the extent to which early life behavior may be predictive of adult cognition. (PsycInfo Database Record (c) 2026 APA, all rights reserved).