Effect of glutamate and antagonists of N-methyl-D-aspartate receptors on experimental parkinsonian syndrome in rats.

Intranigral administration of glutamate to rats with parkinsonian syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine augmented the development of parkinsonian symptoms (oligokinesia and muscular rigidity), but did not affect motor activity of intact animals. Memantine administered intraperitoneally in parallel with induction of parkinsonian syndrome weakened the development of oligokinesia and muscular rigidity in a dose-dependent manner starting from 5 mg/kg and abolished toxic effect of glutamate. Ketamine (15 mg/kg) under the same conditions less potently prevented the development of oligokinesia, did not prevent the development of muscular rigidity, and did not antagonize glutamate toxicity. The data attest to an important role of glutamate and activation of N-methyl-D-aspartate receptors in the induction and development of parkinsonian syndrome.