ETHANOL ELEVATES FETAL SERUM GLUTAMATE LEVELS IN THE RAT

Glutamate is an important excitatory neurotransmitter. However, a sust ained elevation of glutamate in the extracellular space may be toxic t o neurons. Because the blood-brain barrier is incomplete in the develo ping fetus, an elevation of fetal serum glutamate could expose the imm ature, growing brain to potentially toxic revels of extracellular glut amate. Chronic ethanol consumption during pregnancy is associated with an increased risk for a complex array of congenital anomalies, includ ing alterations in the CNS, a hallmark of the fetal alcohol syndrome. Some central nervous system changes appear to involve the glutamate re ceptor, including reduced number and altered function. One mechanism f or receptor downregulation may be a sustained elevation in extracellul ar glutamate. We hypothesize that chronic ethanol exposure during preg nancy leads to an elevation in fetal serum glutamate. When rats were f ed ethanol-containing liquid diet throughout pregnancy, growth retarda tion of fetuses was observed at sacrifice (gestation day 20). Within e ach group, ethanol-fed, pair-fed, and ad libitum chow-fed, serum gluta mate revels were generally higher in the fetus than in the dam. Ethano l treatment had no effect on fetal or maternal serum glutamine, a reci procal metabolite of glutamate. In contrast, ethanol treatment increas ed serum glutamate levels in the fetal serum by nearly 50%, compared w ith either of the control groups. Maternal serum glutamate was not aff ected. The finding of ethanol-induced elevation of fetal serum glutama te suggests that the developing brain might be concurrently exposed to elevated revels of extracellular glutamate. Chronic exposure to eleva ted glutamate during critical periods of brain development may contrib ute to the pathogenesis of the fetal alcohol syndrome.