Drugs of abuse have become a major health problem. This is particularly true in the population of pregnant women where ingested substances may have an adverse impact on growth and development of the fetus and long- term neurobehavioral function. Cocaine and its derivatives have become the most widespread illegally ingested drug among women of child bearing age. While the pharmacology of cocaine is well known most studies have been based on work in adult animal models. The effects of cocaine in the developing animal and human may be quite different from effects in adults. Fetal and newborn animals exhibit higher circulating catecholamine concentrations and greater dependence on circulating levels than at any other period of development. We will determine the effect of cocaine administration in immature and near-term fetal sheep on circulating catecholamine levels and sympathetic nervous system activity. We will determine the physiological and pharmacological consequences of repetitive fetal cocaine administration. We hypothesize that placental metabolism of catecholamines is critical in maintenance of low circulating fetal catecholamine levels and we will determine if cocaine interferes with that metabolism. We will determine if cocaine potentiates the adverse physiological effects of fetal hypoxia. Our proposed studies to characterize the physiologic and pharmacologic effects of fetal exposure to cocaine will be of importance in understanding the pathophysiology of drugs of abuse during pregnancy.
