A MURINE MODEL OF PRENATAL COCAINE EXPOSURE - EFFECTS ON THE MOTHER AND THE FETUS

To develop and characterize a murine model for investigating the long- term effects of prenatal cocaine exposure. the present study establish ed the route of drug administration and the doses to be used for pregn ant C57BL/6 mice. Comparison of the effects of a high dose of cocaine (60 mg/kg) when gavaged or injected subcutaneously (SC) established pa tterns of pathology characteristic of administration route but no domi nating logic for selecting one over the other route for prenatal studi es; however, because of the fourfold greater brain levels, with no evi dence of greater pathology, the SC route was selected. When injected d aily during gestation days 12-18, the period of prenatal development o f dopamine systems, cocaine at doses producing plasma concentrations c onsistent with its stimulatory effects reduced food ingestion and weig ht gains during pregnancy and fetal body and brain weights at term. Th e extent of these reductions was comparable to reports on babies expos ed to cocaine prenatally. Furthermore, the present study suggests that maternal undernutrition is not a likely mediator of these perinatal e ffects and that differences in the amount of cocaine exposure may caus e the contrasting effects of maternal cocaine noted in the human liter ature. Copyright (C) 1996 Elsevier Science Inc.