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

Abstract

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). Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3g/kg) or maltodextrin daily on embryonic days (E) E8.5 through E17.5. Blood alcohol levels were 211±14mg/dL at 30min post-gavage. Offspring behavior was tested at adolescence. 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(1,54)=2.892, p=0.095]. In the Y-maze, ALC offspring had a higher percent alternation than did controls [F(1,54)=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×minute effect for males [F(4,120)=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(1,53)=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. 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.