Prenatal stress history modifies adolescent stress effects on adult social behavior and basolateral amygdala GABAergic neurons with perineuronal nets.

Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the amygdala, are disrupted by stress and implicated in stress-related psychopathologies. Using a rodent model, the current study investigated the isolated and combined effects of prenatal and adolescent stress on adult social interactions and GABAergic neurons surrounded by perineuronal nets (PNNs) in the basolateral amygdala (BLA). Male and female rats were exposed to chronic variable stressors (CVS) prenatally (PS), during adolescence (AS), or during both prenatal and adolescent periods (PS + AS). In adulthood, all animals were tested for social behavior with same-sex weight-matched partners, and brains were collected for identification of BLA inhibitory neurons (GAD67 staining) and PNNs (Wisteria Floribunda Agglutinin staining). Significant prenatal × adolescent stress interactions were observed for both social behavior and BLA inhibitory neuron measures. For social behavior, AS alone increased social investigation in adulthood relative to non-stressed (NS) controls and animals exposed to combined PS + AS. PS + AS subjects did not significantly differ from NS controls, suggesting that prenatal stress exposure prevented adolescent stress-induced increases in adult social investigation. An analogous data pattern was observed in the BLA. AS alone significantly decreased the number of GAD67 + neurons surrounded by PNNs (co-labeled) relative to NS controls and showed a trend toward a decrease relative to combined PS + AS (p = 0.07). The number of co-labeled cells did not differ between combined PS + AS and NS controls. Assessment of the percentage of total GAD67 + neurons co-labeled with PNNs revealed that PS alone reduced the proportion of GAD67 + neurons surrounded by PNNs, while AS alone showed a trend toward reduction (p = 0.06). Combined PS + AS did not alter this measure relative to NS controls. Overall, these findings support a developmental interaction model in which prenatal stress alters the impact of adolescent stress on both BLA inhibitory neuron-associated perineuronal nets and adult social behavior.