Early-life adversity induces social anxiety and cognitive deficits alongside neurobiological changes in rats

Mood disorders such as anxiety often originate early in life, yet rodent models of early-life adversity are typically assessed only in adulthood using a limited array of behavioral assays. Here we show how neonatal isolation affects social behavior, learning and memory, neuron structure, and blood metabolites in Long Evans rats ( Rattus norvegicus ). Juvenile isolated rats play less with unfamiliar peers but interact typically with cage mates, consistent with a social anxiety-like phenotype. As adults, isolated rats show reduced cooperation and increased aggression, whereas traditional anxiety tests do not reveal increased generalized anxiety. Females show pronounced cognitive and motivational deficits. Isolation is also associated with reduced dendritic spine density in the medial prefrontal cortex, sex-specific neuronal changes in the dorsolateral septum, and shifts in glucose and amino acid metabolism. Together, these findings reveal selective, sex-dependent consequences of early-life social deprivation across behavioral, neural, and metabolic domains.