Neonatal alcohol exposure augments voluntary ethanol intake in the absence of potentiated anxiety-like behavior induced by chronic intermittent ethanol vapor exposure.

Individuals fetally exposed to alcohol have a disproportionate risk for developing lifetime alcohol dependence, an association that may be confounded by the presence of comorbid conditions, such as anxiety. Anxiety is also observed following fetal alcohol exposure and is known to exacerbate ethanol consumption, highlighting the utility of animal models to assess this relationship. The present study evaluated the impact of third-trimester equivalent ethanol exposure on ethanol consumption and anxiety-like, marble burying behavior in adult, male C57BL/6 mice following exposure to chronic intermittent ethanol vapor, proposed to model dependence. Neonatal mice (P5-6, 2.5-3.0 g) were administered one injection of saline or ethanol (2.5 g/kg, subcutaneously [s.c.]). Pre-vapor marble burying and limited-access two-bottle choice ethanol intake (15% v/v, 2 h) were comparable in adults (8 weeks of age) across neonatal treatment groups. Five consecutive drinking sessions were repeated 72 h after each weekly ethanol vapor exposure procedure for a total of five vapor/drinking cycles. Consistent with prior research, an increase in voluntary ethanol drinking was observed in vapor-exposed, neonatal saline-treated mice throughout the study starting after the second vapor cycle compared to both air-exposed control groups. In neonatal ethanol-treated mice, this increase in ethanol intake and preference following vapor exposure was accelerated, being observed after the first vapor cycle, and observed at an augmented level compared to vapor-exposed, neonatal saline-treated mice and air controls for both neonatal conditions. Conversely, marble burying was enhanced equivalently in vapor-exposed mice from either neonatal treatment group relative to their respective air-exposed controls. These data recapitulate clinical observations of enhanced sensitivity for alcohol dependence following developmental alcohol exposure, which may reflect enhanced motivational drive rather than potentiated negative affect. The present model will facilitate the future exploration of mechanisms that underlie increased risk for alcohol use after early developmental exposure.