Methamphetamine concentrations in fetal and maternal brain following prenatal exposure.
Levels of methamphetamine in maternal striatum and whole fetal mouse brain were assessed at 0.5, 1, 2, and 4 h postinjection on gestational day 14 (GD14) following a single, subcutaneous injection of 40 mg/kg (+)-methamphetamine hydrochloride to pregnant mice. In the dams, striatal concentrations of methamphetamine peaked at 1 h postinjection, reaching levels of approximately 510 ng/mg protein. Amphetamine, the primary metabolite of methamphetamine, increased to 77 ng/mg protein at 2 h and remained elevated by 4 h postinjection. In the fetal brain, peak methamphetamine concentrations of approximately 122 ng/mg protein were attained at 1 h. Amphetamine was only detectable in fetal brain at 2 and 4 h postinjection. Regional analysis of methamphetamine levels in fetal striatum, cortex, and brainstem revealed that the drug was not uniformly distributed. Maternal administration of methamphetamine results in fetal brain drug concentrations, which approximate those reported in human infants whose mother abused methamphetamine. This dosage regimen, therefore, serves as an appropriate animal model for assessing the potential risks to human offspring exposed to methamphetamine in utero.
Won
L
L
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, 947 East 58th Street, Chicago, IL 60637, USA.
Bubula
N
N
McCoy
H
H
Heller
A
A
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D007700:Kinetics; D008694:Methamphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014018:Tissue Distribution
D008694:Methamphetamine