The incidence of cocaine abuse has increased dramatically within recent years. Probably one of the more frightening statistics suggest that cocaine may be one of the most frequently abused drugs by pregnant women suggesting that the number of cocaine-exposed infants may be increasing. The available data suggest that prenatal cocaine exposure may have adverse effects on the developing offspring. The purpose of this proposal is to develop a rodent model to look at the effects of cocaine exposure during the equivalent of the human third trimester. This is a period of rapid central nervous system (CNS) growth and proliferation commonly referred to as the """"""""brain growth spurt"""""""". There are data that suggest that this period may be particularly sensitive to cocaine-induced effects on the CNS. In rats, the analogous developmental period occurs during the first two weeks after birth. Therefore, in order to study the effects of cocaine exposure during the third trimester of human pregnancy, cocaine must be administered to the neonatal rat. To administer cocaine neonatally, an artificial-rearing procedure will be employed by which the pups are implanted with an intragastric cannula and fed a milk formula which the pups are implanted with an artificial-rearing procedures will be employed by which the pups are implanted with an intragastric cannula and fed a milk formula with the drug added to the formula. A major advantage of this artificial-rearing method is that the amount of food consumed daily is controlled by the experimenter thus allowing complete control over cocaine exposure without any risk of concomitant undernutrition. Following the establishment of appropriate doses (a low and a high dose will be chosen following the establishment of appropriate doses (a low and high dose will be chosen following a dose-response study), a number of behaviors will be examined. Since there are preliminary data suggesting that cocaine-exposed infants exhibit motor and balance deficits, a number of tasks that assess motor development, coordination and balance will be examined. In addition, suckling behavior and associative learning will be assessed. Finally, since the catecholaminergic system undergoes a substantial amount of growth and proliferation during this """"""""brain growth spurt"""""""", pharmacological challenges which assess the functional integrity of the catecholaminergic system will be examined. These findings could provide important information regarding the sensitivity of the CNS to cocaine during the third trimester. If this developmental period is particularly sensitive to cocaine injury (as is predicted), these findings would provide further evidence of the importance of drug treatment and education during pregnancy.
