The enduring impact of neurulation stage alcohol exposure: A combined behavioral and structural neuroimaging study in adult male and female C57BL/6J mice

Prenatal alcohol exposure (PAE) can cause behavioral and brain alterations over the lifespan. In animal models, these effects can occur following PAE confined to critical developmental periods, equivalent to the third and fourth weeks of human gestation, before pregnancy is usually recognized. The current study focuses on PAE during early neurulation and examines the behavioral and brain structural consequences that appear in adulthood. On gestational day 8 C57BL/6J dams received two alcohol (2.8 g/kg, i.p), or vehicle, administrations, four hours apart. Male and female offspring were reared to adulthood and examined for performance on the elevated plus maze, rotarod, open field, Morris water maze, acoustic startle, social preference (i.e. three-chambered social approach test), and the hot plate. A subset of these mice was later evaluated using magnetic resonance imaging to detect changes in regional brain volumes and shapes. In males, PAE increased exploratory behaviors on the elevated plus maze and in the open field; these changes were associated with increased fractional anisotropy in the anterior commissure. In females, PAE reduced social preference and the startle response, and decreased cerebral cortex and brain stem volumes. Vehicle-treated females had larger pituitaries than did vehicle-treated males, but PAE attenuated this sex difference. In males, pituitary size correlated with open field activity, while in females, pituitary size correlated with social activity. These findings indicate that early neurulation PAE causes sex specific behavioral and brain changes in adulthood. Changes in the pituitary suggest that this structure is especially vulnerable to neurulation stage PAE.