Growth and behavioral differences in a C57BL/6J mouse model of prenatal alcohol exposure

Background. Prenatal alcohol exposure (PAE) can produce behavioral deficits in the presence or absence of growth and morphological deficits. Here, we describe a murine PAE model having parallels to the clinical diagnosis of alcohol-related neurodevelopmental deficit (ARND). Methods. Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or maltodextrin daily on embryonic days (E) E8.5 through E17.5. Blood alcohol levels were 211 +/- 14 mg/dL at 30 min post-gavage. Offspring behavior was tested at adolescence. Results. ALC dams gained less weight during the alcohol exposure period (p = 0.035). ALC male and female pups weighed more than controls at P15 (p < 0.001) and P22 (p < 0.001), but not at P37, perhaps because their dams were pair-housed. During the training session for accelerating rotarod, control offspring trended to stay longer on the rotarod than did ALC offspring [F-(1,F-54) = 2.892, p = 0.095]. In the Y-maze, ALC offspring had a higher percent alternation than did controls [F-(1,F-54) = 16.577, p < 0.001], but activity level did not appear to differ. In the fear-conditioning test, there was no ALC effect in the training trial. In the contextual test, there was a group x minute effect for males [F-(4,F-120) = 2.94, p = 0.023], and ALC trended to freeze less than controls in minute 1 (p = 0.076) and froze less in minute 2 (p = 0.02). In the cue test, there was a trend for a group-sex interaction [F-(1,F-53) = 3.008, p = 0.089] on overall freezing, such that ALC males (p < 0.05) again froze less than control males, whereas ALC females (p < 0.05) froze more than control females. Conclusions. This mouse model of PAE, using a repeated intermediate exposure, produces modest behavioral impairments that are consistent along the continuum of PAE models, including deficits in associative memory and hyper-responsivity. The lack of growth or morphological deficits suggests these mice may model aspects of ARND. (C) 2021 Elsevier Inc. All rights reserved.