This is a proposal for a program project that would employ an animal model to investigate the consequences of fetal exposure to cocaine and the mechanisms by which observed deficits are produced. Recent clinical reports indicate that children born to cocaine-using women not only display a number of abnormalities as neonates but also demonstrate a number of behavioral abnormalities years later. The clinical symptoms that have been observed in such children suggest long-term disruption in the sensory processing of stimuli, cognitive abilities, emotionality and motor activity. Current knowledge of brain function suggests that the adequate. Expression of such behaviors requires the integrity of cortical, limbic and extrapyramidal structures. The pharmacology of cocaine suggests that it could have both direct and indirect effects on the development of these brain regions through actions on monoamines and opioid peptides. The possibility that the behavioral abnormalities might be due to measurable alterations in the structure and function of these brain regions will be examined in five interactive projects that will cover various developmental periods from mid-gestation to adulthood. Each project will test specific hypotheses that predict the occurrence of cocaine induced abnormalities as measured by behavioral, physiological, anatomical, pharmacological, neurochemical and molecular analyses. A core facility will be established to assure a consistent program of housing, breeding, administration of cocaine or vehicle to the pregnant dams, measurement of plasma and brain content of cocaine in dam and fetus, determination of any abnormalities in the neonate, cross fostering of neonates, paired feedings when appropriate, neurological and behavioral assessment of some developmental landmarks and adequate supply of animals at various ages. The exposure to cocaine and thus establish an animal model that be employed to develop method for the treatment and prevention of such abnormalities in children.
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