Children born of mothers who drink alcohol during their pregnancies can be afflicted with syndrom of morphological anomolies of varying severity and of behavioral dysfunctions ranging from profound mental retardation to hyperactivity to subtler marginal deficits. The behavioral effects of prenatal alcohol exposure in children have been modeled reliably by administrating pregnant rats liquid diets containing different percentages of ethanol-derived calories (35% or 0% EDC). The model produces pups in which maturational delays and deficits in activity and learning have been studied successfully. The biological, and in particular, neurochemical bases for the behavioral effects of prenatal alcohol exposure are not well understood. We intend to investigate the functional integrity of central nervous system neurotransmitter systems in these animals by measuring the development of their behavioral responses to pharmacological agents. Specifically, our aim is to study the influence of prenatal alcohol exposure on behaviroal responses to drugs which influence dopamine, norepinephrine and acetylcholine systems. In particular, the pharmacological treatments chosen will be used because they are known to influence various measures of locomotor activity, display well-defined developmental courses, and have relatively well-understood mechanisms of action. The results of the proposed experiments, first, will provide important information with which to characterize the functional effects of prenatal alcohol exposure on neurotransmitter systems. Secondly, results which show attenuated behavioral effects of prenatal alcohol exposure in the animal model may suggest possible therapeutic treatments for children with symptoms of fetal alcohol exposure. Thirdly, these pharmacological challenges may reveal subtle or marginal deficits and thereby may prove useful in determining the range of influence of prenatal alcohol exposure. In summary, the proposed experiments will utilize a reliable animal model of the behavioral effects of prenatal alcohol exposure in children to study the symptomatic contribution and funcitonal integrity of neurotransmitter systems in """"""""Fetal Alcohol Syndrome."""""""" The nature and developmental course of specific psychopharmacological responses wil be tested. The results of this research will provide important information on the developmental courses of specific behaviors after prenatal alcohol exposure, on the nature of relatively specific neurotransmitter involvement in the behavioral changes, and on the possible diagnostic and therapeutic uses of these pharmacological challenges.
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