Development under the influence of cocaine. I. A comparison of the effects of daily cocaine treatment and resultant undernutrition on pregnancy and early growth in a large population of rats

Abstract

After administering cocaine to pregnant and lactating dams in oral dosages ranging from 5 to 90 mg/kg/day, we observed a slight increase in fatalities starting at 60 mg/kg/day, followed by a sharp rise fatalities at higher dosages. Therefore, a dosage near 60 mg/kg/day by the oral route appears to mark a useful threshold between highly lethal dosages and an acceptable, sublethal dosage for chronic studies of pregnant rats. At 60 mg/kg/day, there was a marginal trend toward less weight gain in the cocaine-treated dams during pregnancy, followed by a much more pronounced lag in weight recovery following parturition. Neither prematurity nor any reduction in litter sizes and birth weights was consistently observed at dosages below 90 mg/kg/day; however, poor maternal care was evident when the dams received dosages of 80-90 mg/kg/day, producing a very high death rate in the neonatal offspring. Internal bleeding (intracranial and subcutaneous) was also observed in three neonates whose dams received cocaine at rates of 60-90 mg/kg/day, confirming a similar clinical observation and indicating a direct action of cocaine toxicity on the fetus. Although fetal growth and development were not significantly altered by administering the pregnant dams 60 mg/kg/day, there was a higher death rate in the offspring during the initial 24 hr after delivery. Weight gain appeared transiently retarded early in the suckling period, although similar growth retardation was observed in the offspring of pair-fed controls. These results indicate that the dam's undernourishment contributes much to the early growth retardation resultant from cocaine administration. The most striking effect of cocaine on the offspring, after considering undernourishment, appears to be an increased mortality in the neonatal period (60 mg/kg/day and higher), apparently resulting from poor maternal care. The greatest risk of all was the death of the dam at any point beginning with the second administration of cocaine at 60 mg/kg/day and increasing precipitously at any higher dosage.