A substantial amount of clinical evidence indicates that alcohol during pregnancy can produce morphological and behavioral abnormalities in offspring. Animal studies have confirmed these observations under nutritionally and environmentally controlled conditions unattainable in the humans and have established ethanol exposure as the most likely causative agent. In addition, the animal studies indicate that some of the behavioral deficits can extend to the fully mature adult. Research from our project established that C57BL/6 mice exposed to ethanol prenatally had reduced body weight and several behavioral deficits postnatally including impaired short term memory and an inappropriate response to positive reinforcement. Since this strain is also susceptible to the teratogenic effects of ethanol, it appears to provide a comprehensive rodent model for studying the effects of prenatal alcohol exposure. Included among the postnatal effects of prenatal alcohol exposure in our studies were three results distinguishable from previous reports and are the basis for the proposed research. First, prenatal ethanol exposed mice had weight reductions which were not manifest until around the time of weaning and lasted into adulthood; second, their behavior was less influenced than controls by positive reinforcement or by ethanol; and third, they were less able than controls to discriminate the systemic presence of ethanol. Both effects persisted into adulthood and are likely permanent. The studies described in this proposal are to characterize these effects and investigate potential mediating mechanisms. Currently there is no evidence for these findings in humans prenatally exposed to ethanol. Due to the time lapse between prenatal exposure and the manifestation of these effects it is doubtful that such investigations would be undertaken unless prompted by the results of animal experiments. It is hoped that the proposed studies will help establish the conditions under which these phenomena occur and a possible mechanism for each thus provide the stimulus for similar investigations in humans.
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