Analysis of the synergy between prenatal ethanol and postnatal adolescent ethanol exposure

Prenatal ethanol exposure (PEE) is associated with long-lasting neurodevelopmental alterations that increase susceptibility to adverse behavioral outcomes, including greater likelihood of binge drinking during adolescence. However, the interactive effects of these two developmental risk factors remain underexplored. The present study investigated the synergistic impact of PEE and adolescent binge-like ethanol exposure on behavioral and ethanol consumption patterns in Wistar rats. Pregnant dams received ethanol (2.0 g/kg/day) or vehicle from gestational days 17-20. Offspring were subjected to intermittent ethanol exposure (4.0 g/kg/day, two days on-two days off) or vehicle from postnatal days 23-36. Behavioral assessments included tests for anxiety-like behaviors (light-dark box test), anhedonia (sucrose preference test), exploratory behavior (multivariate concentric square field test), and voluntary ethanol consumption in early adulthood. PEE was associated with increased overall fluid consumption (p = 0.001, η²p = 0.17) and a sex-dependent increase in ethanol intake (p = 0.001, η²p = 0.05). PEE rats displayed reduced sucrose preference (p = 0.02, η²p = 0.07), suggesting an anhedonic-like phenotype independent of adolescent ethanol exposure. The latter exposure induced an anxious phenotype, characterized by reduced time in the illuminated compartment of the light-dark box test, which was attenuated in PEE-exposed rats (p = 0.03, η²p = 0.06). These findings suggest that PEE (a) facilitates ethanol consumption in offspring, potentially through tolerance mechanisms or altered chemosensory processing; and (b) modulates anxiety-like behaviors induced by adolescent ethanol exposure. Understanding these interactions is critical for elucidating the mechanisms underlying alcohol use disorders and designing targeted interventions for at-risk populations.