Bolus maternal cocaine administration does not produce a large increase in fetal sheep cerebral cortical glutamate concentration.
Human cocaine use during pregnancy may result in postnatal neurologic dysfunction and abnormal behavior. L-Glutamate, the major excitatory neurotransmitter in the brain, plays an important role in cerebral cortical development. An optimal level of glutamate is required for normal neuronal development. We tested whether acute cocaine exposure produces large increases in glutamate release in the intact cerebral cortex of the near-term fetal sheep. Cocaine 3.0 mg kg(-1) IV bolus produced the expected increase in maternal and fetal mean arterial pressure, increase in fetal heart rate, decrease in uterine blood flow, and decrease in fetal arterial blood pO2 (N = 5). The percentage increases in extracellular glutamate concentration in the fetal cerebral cortex measured by in utero microdialysis were 7%, 15%, 17%, 17%, and 43% in each fetus (upper 95% confidence bound for the median = 43%). We conclude that if cocaine increases glutamate concentration in the developing cerebral cortex, the increase in magnitude is small relative to the changes produced by other interventions such as ethanol or umbilical cord occlusion. Mechanisms other than increases in cerebral cortical glutamate concentration probably contribute to the neurologic injury associated with prenatal cocaine exposure.
Penning
D H
DH
Department of Anesthesiology, Duke University, Durham, NC, USA. penni008@mc.duke.edu
Dexter
F
F
Henderson
J L
JL
Chestnut
D H
DH
Reynolds
J D
JD
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006340:Heart Rate, Fetal / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000098:blood supply
D018765:Dopamine Uptake Inhibitors; D018698:Glutamic Acid; D003042:Cocaine