Double hit model of prenatal alcohol exposure and adolescent intermittent alcohol exposure modulates transcriptional plasticity and perineuronal-net organization in the male rat brain

Prenatal alcohol exposure (PAE) and adolescent alcohol intermittent exposure (AIE) may interact to produce brain changes in areas involved in reward and emotion. Evidence for these interactive effects remains, however, preliminary. This preclinical study examined independent and combined effects of PAE and AIE on ΔFosB immunoreactivity and perineuronal nets (PNNs) in male Wistar rats, in mesocorticolimbic areas. Pregnant dams received ethanol (2,0 g/kg) or water on gestational days 17–20. Male adolescent offspring were given AIE (4,0 g/kg/day) or water across eight sessions (postnatal days 25–38). On postnatal day 42, ΔFosB immunoreactivity was quantified in the prelimbic cortex (PrL), nucleus accumbens core and shell, dorsomedial (DMS) and dorsolateral striatum, basolateral amygdala (BLA), and capsular central amygdala (CeC). PNNs were assessed by Wisteria floribunda agglutinin (WFA) staining in the BLA and PrL. AIE increased ΔFosB immunoreactivity in the DMS, BLA, and CeC (p<.05). In the BLA, analysis of ΔFosB expression revealed a significant PAE×AIE interaction (p<.005). PAE significantly increased the number of BLA cells surrounded by PNNs. The PAE×AIE interaction for heightened BLA PNN+ cells did not reach significance (p=.08, n2p=.24). The findings indicate that AIE produces regionally selective ΔFosB induction and that PAE amplifies this effect at BLA. Developmental ethanol may alter transcriptional plasticity and PNN organization within amygdalostriatal areas.