A Model to Explain Learning Deficits Following Prenatal Alcohol Exposure

Despite warning labels, some pregnant women continue drinking alcohol, putting the developing fetus in danger. Fetal Alcohol Spectrum Disorders (FASDs) are caused by heavy drinking during pregnancy and are marked by a range of behavioral and neurocognitive problems, including learning and memory deficiencies, with significant variability in the clinical population. We hypothesized that the effects of alcohol on the developing fetus, such as those seen in FASDs, can be exacerbated by hypoxia (reduced oxygen flow). Hypoxia is a common occurrence during birth as the offspring exits the birth canal and has a limited source of oxygen; therefore offspring with a previous history of prenatal alcohol exposure may be at increased risk for learning deficits. We tested this hypothesis using our rodent model. Male and female Sprague-Dawley rat pups were exposed to either: alcohol (4.5 g/kg/day on postnatal days (PND) 1 - 7), intubated control, or non-treated control (this overlaps the human 3rd trimester brain growth spurt). On PND 8, rats were either exposed to control air or a brief hypoxic challenge (8.5 min). These offspring were tested during adolescence (PND 40 and 41) in a water maze to assess spatial learning. The alcohol and hypoxia exposed males took longer to learn the task than all other groups. Surprisingly, females were not impaired. These results suggest that the combination of alcohol exposure and hypoxia can increase the deficits caused by fetal alcohol exposure and that there may be sex differences in sensitivity on some measures. Further work is needed to understand this sex difference, the underlying mechanisms, and possible ways to reduce these effects. Supported in part by NIAAA 017956 to SB.