Consequences of Prenatal Ethanol Exposure and Maternal Stress on Offspring

Extensive evidence in humans suggests that exposure to insults during gestation, such as ethanol or maternal stress, can negatively impact the developing fetus in manners which can last into adulthood. These deleterious effects can include various behavioral challenges including cognitive impairments and increases in anxiety. These findings have been replicated in animal models of prenatal ethanol exposure and prenatal stress exposure, but little work has been conducted on measuring the interactive effects of the two prenatal insults in combination. Currently, there is no animal model of combined prenatal ethanol and prenatal stress exposures which has been utilized to systematically evaluate the potential interactive effects of the two gestational insults on adult offspring behavior and expression of biochemical markers of activity-dependent synaptic plasticity. Based on previous literature, it is believed that maternal stress will potentiate the prenatal ethanol induced learning deficits on a hippocampally- sensitive task, as well as potentiate the reduction in expression of biochemical markers of activity-dependent dentate gyrus synaptic plasticity. The model developed here employed a previously described voluntary ethanol consumption model and a novel predator scent exposure paradigm, resulting in no significant deficits in maternal weight gain, maternal ethanol consumption, maternal stress reactivity, maternal care of litters, number of pups per litter, nor the amount of weight gained from birth to weaning in the pups. Exposure to prenatal ethanol resulted in a significant decrease in learning in a trace fear conditioning task, and prenatal stress exposure resulted in heightened anxiety as measured by performance in the elevated plus maze. However, the two insults did not interact to worsen either outcome. Assessment of ARC protein expression, a marker of neuronal activity, and AMPA receptor subunit expression, indicated a significant elevation in basal expression of ARC protein and a significant reduction in GluA1 subunit expression in the dentate gyrus of animals prenatally exposed to one or both insults as compared to non-exposed animals, as well a significant elevation in GluA1 and 2 following training in the trace fear conditioning task in non- exposed animals, but absent in all other groups. It is possible that the basal elevations in ARC expression could be the result of a compensatory up- regulation of neuronal activity in prenatally exposed animals, which results in the endocytosis of AMPA receptors from the cellular membrane. The reduction of AMPA receptors could explain, in part, the significant deficits in hippocampal- sensitive learning in animals exposed to prenatal ethanol. Future directions following this work should include assessments of male offspring, electrophysiological characterization, and inquiry into the potential for amelioration of the learning deficits by ampakine administration