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-HCI: 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 micrograms/g [corrected] 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 micrograms/g [corrected]. 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.
Miller
S R
SR
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston 29425-0742, USA.
Middaugh
L D
LD
Boggan
W O
WO
Patrick
K S
KS
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003903:Deuterium; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012044:Regression Analysis; D013997:Time Factors
D003903:Deuterium; D003042:Cocaine