Dose-dependent consequences of cocaine on pregnancy outcome in the Long-Evans rat

Abstract

The number of obstetric patients abusing cocaine has increased dramatically in recent years. To better understand its effect on pregnancy and to establish the LD50s for maternal and fetal fatalities, the dose-dependent effects of cocaine on pregnancy outcome were investigated in the Long-Evans rat. Pregnant animals were given either saline or 40, 50, 60, 70, 80, or 90 mg/kg cocaine hydrochloride from gestation days 7 to 19 inclusive. An additional group was non-treated and had ad lib access to food and water. Animals were sacrificed on gestation day 20 and the fetuses were examined. Despite treatment during the major periods of organogenesis and brain development, few congenital abnormalities were observed. There were, however, dose-dependent effects on maternal weight gain, maternal food and water consumption, fetal weight, maternal and fetal fatalities, fetal edema, abruptio placentae and cephalic hemorrhages. Despite suppression of maternal weight gain, there was preservation of fetal weights at cocaine doses up to and including 80 mg/kg/day, suggesting some protection of fetal growth. In addition to providing information on the gestational effects of cocaine in the rat, the present study provides information useful in guiding the selection of cocaine doses for subsequent behavioral teratology studies.