Prenatal cocaine exposure in the Long-Evans rat: I. Dose-dependent effects on gestation, mortality, and postnatal maturation.

Pregnant Long-Evans rats were injected daily with 40, 60, 80, or 100 mg/kg cocaine HCl (SC, 2% solution) from gestational days 7-20 (sperm positive = day 0). Daily doses were split evenly with half given between 9:00-10:00 a.m. and half between 3:00-4:00 p.m. An ad lib-fed group as well as nutritional control groups that were pair-fed to the 80 and 100 mg/kg cocaine dams were also evaluated (N = 11-18 liters/group). Cocaine had no effect on gestational length but did cause dose-dependent decreases in maternal food consumption and weight gain and increases in maternal mortality. Interestingly, cocaine-treated dams shows a significant increase in water consumption. In terms of offspring variables, there was a dose-dependent decrease in birth weight and postnatal weight gain in both the cocaine and pair-fed groups. There were also dose-dependent effects on litter size, stillbirths and postnatal mortality in the cocaine-treated groups as compared to the control groups. High dose cocaine treatment caused delays in several indices of physical maturation (pinna detachment, fur growth, ear opening, eye opening, vaginal opening) but not in others (incisor eruption, testicular descent). Physical anomalies and postnatal morbidity, while uncommon, were observed in animals prenatally exposed to the higher cocaine doses. Collectively, these data suggest that prenatal cocaine exposure can increase postnatal morbidity as well as increase pre-and postnatal mortality in animal offspring.