Cocaine concentrations in fetal C57BL/6 mouse brain relative to maternal brain and plasma

Cocaine concentrations in maternal plasma and brain and fetal brain of mice were evaluated as a model for fetal brain exposure during maternal cocaine use. On days 12–18 of gestation, mice (C57BL/6; N = 5–7/group) received SC cocaine-HCl: 20 or 40 mg/kg. Maternal plasma and brain (accumbens and caudate nuclei removed), and fetal brain were collected at 0.5, 1, and 2 h following the last injection. Analysis was by GC-MS. Brain cocaine levels in the dams declined from 9.6 to 3.4 and 20.9 to 12.5 mg/g during the 0.5–1-h period after the low and high doses, respectively, and were 7.5–14.3 times greater than plasma levels. The corresponding fetal brain concentrations changed from 1.6 to 1.3 and 2.9 to 3.4 mg/g. By 2 h, brain cocaine concentrations in dams declined to approximately 10% of their 0.5-h values, with a slower drug decay occurring in fetal brain. Maternal plasma cocaine concentrations correlated with those of maternal brain (r = 0.94, p < 0.01) and fetal brain (r = 0.69, p < 0.01). The present results indicate that cocaine accumulates to a lesser extent in fetal brain than in maternal brain of C57BL/6 mice; however, the duration of exposure appears to be more sustained in the fetus, a phenomenon that may have toxicological implications for human in utero cocaine exposure.