Clinical studies have shown that in utero alcohol exposure can result in morphological and behaviorally teratogenic effects (the fetal alcohol syndrome, FAS). However, despite relatively similar levels of in utero alcohol exposure, not all children are born with FAS. Determination of risk factors, in addition to alcohol, that contribute to the FAS are thus of potential clinical importance. Detailed studies by this investigator have demonstrated the feasibility of using the rat as an """"""""animal model"""""""" to study various factors associated with the fetal alcohol syndrome, e.g., critical levels of prenatal exposure to alcohol, """"""""sensitive periods"""""""" during development, and certain maternal factors e.g., age, parity. The studies to be undertaken in this proposal are a continuation of our exploration of maternal risk factors and deal with the interaction of alcohol and lead and alcohol and Valium during gestation. Such studies are of importance since they may shed light on critical maternal risk factors that may interact with in utero alcohol exposure to affect the severity of the impact of fetal alcohol exposure. In the first series of studies, pregnant rats will be intubated with alcohol, lead or alcohol plus lead. Dose response relations will be determined for these combinations. Controls will be pair-fed/watered. Offspring will be examined postnatally for behavioral anomalies resulting from such exposure and we will determine if exposure to the combination of alcohol and lead results in effects greater than the additive effects of these compounds. In the second series, pregnant rats will be intubated with alcohol, Valium, or alcohol plus Valium. A similar methodology for drug administration and evaluation will be conducted as in the previous experiments. The reason for these combinations is that lead is an ubiquitous environmental pollutant and Valium is the most widely prescribed medication for women of childbearing age. Thus, women who drink will undoubtedly be exposed to one or both substances and there is a possibility of synergism. This may explain why some women are more at risk for fetal alcohol syndrome than others, despite equal consumption of alcohol during pregnancy. FAS is now considered to be the third most commonly recognized disorder of known causation in which mental deficiency is a prominent feature. The present proposal will provide valuable information for the etiology of FAS and also for mental retardation in general.
