Chronic methionine sulfoximine administration reduces synaptosomal aspartate and glutamate in rat striatum

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Methionine sulfoxime (MS) is an inhibitor of glutamine synthetase, an astroglial enzyme believed to be involved in the maintenance of glutamine, a major precursor for neurotransmitter pools of the excitatory amino acids aspartate and glutamate in striatal afferent axon terminals. MS was infused for 7 days (24 micrograms/day) into the lateral cerebral ventricle of rats. On the side of MS infusion, there was a decrease of striatal synaptosomal aspartate (61%), glutamine (63%), and glutamate (48%), while taurine and gamma-aminobutyrate were unaltered when compared to vehicle-treated rats. The results indicate that chronic MS infusion is an effective means by which neurotransmitter aspartate and glutamate levels can be selectively reduced in the striatum.