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

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.