Bolus maternal cocaine administration does not produce a large increase infetal sheep cerebral cortical glutamate concentration

Human cocaine use during pregnancy may result in postnatal neurologic dysfu nction and abnormal behavior. L-Glutamate, the major excitatory neurotransm itter in the brain, plays an important role in cerebral cortical developmen t. An optimal level of glutamate is required for normal neuronal developmen t. We tested whether acute cocaine exposure produces large increases in glu tamate 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 a nd fetal mean arterial pressure, increase in fetal heart rate, decrease in uterine blood flow, and decrease in fetal arterial blood pO(2) (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%). W e conclude that if cocaine increases glutamate concentration in the develop ing cerebral cortex, the increase in magnitude is small relative to the cha nges produced by other interventions such as ethanol or umbilical cord occl usion. Mechanisms other than increases in cerebral cortical glutamate conce ntration probably contribute to the neurologic injury associated with prena tal cocaine exposure. (C) 1999 Elsevier Science Inc. All rights reserved.