Children of women who drink alcohol during their pregnancies can have facial anomalies, growth retardation, and wide-ranging central nervous system (CNS) dysfunction(s). These attentional, cognitive and behavioral problems are the most common and persistent Alcohol-Related Birth Defects (ARBDs). Although Fetal Alcohol Syndrome (FAS) and ARBDs are thought to be the most common theoretically preventable causes of developmental disabilities in the Western world, little, if any, systematic information is available on treatment for FAS/ARBDs. This project will use a valid rodent model of ARBDs to study psychopharmacological responses to CNS stimulants - drugs used to treat hyperactivity and attentional deficits in children. The proposed research will test the ability of, for example, Ritalin, Dexadrine and Cylert to attenuate the effects of in utero alcohol exposure on hyperactivity, attention, and learning and memory in rats. The proposed studies will expand upon our previous work showing altered responses to drugs acting on CNS dopamine neurotransmitter systems. Specifically, we will use rats exposed prenatally to alcohol to assess age- and gender- influenced: 1. Behavior in tasks sensitive to attentional dysfunction; 2. Attenuation of behavioral, attentional and cognitive deficits with CNS stimulants; and 3. Changes in the functional status of specific components of CNS dopamine systems - systems which mediate the therapeutic action of the CNS stimulants. The results of the proposed studies will indicate the ability of CNS stimulants to attenuate some of the behavioral sequelae of prenatal alcohol exposure. Challenges with selective dopaminergic drugs will also indicate the nature and site of specific CNS changes that may underly these deficits. Finally, these studies will facilitate attaining our long-term goal to identify potential pharmacological treatments for children with FAS/ARBDs.
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