l-701324 and Parkinson-Disease

The aim of the study was to examine the effect of antagonists of the NMDA receptor on the parkinsonian-like muscle rigidity in rats. Reserpine and haloperidol increased the muscle resistance of the hind foot to passive movements, as well as the reflex electromyographic (EMG) activity in the gastroenemius and tibialis anterior muscles. MK-801 (0.32-1.28 mg/kg s.c.), an uncompetitive antagonist of the NMDA receptor, and L-701,324 (5-40 mg/kg i.p.), an antagonist of the glycine site, reduced the muscle tone and the reflex EMG activity enhanced by reserpine or haloperidol. AP-5 (2 and 5 micrograms/0.5 microliter), a competitive antagonist of the NMDA receptor, and 5,7-dichlorokynurenic acid (1.0-4.5 micrograms/0.5 microliter), the glycine site antagonist injected bilaterally into the rostral striatum, inhibited the muscle rigidity induced by haloperidol. In contrast, AP-5, injected alone bilaterally into the intermediate-caudal striatum induced muscle rigidity. The present results suggest that: (1) the inhibitory effect of the NMDA receptor antagonists on the parkinsonian-like muscle rigidity depends, at least partly, on their action on the rostral striatum; (2) the blockade of NMDA receptors in the intermediate-caudal striatum may reduce the beneficial impact of these compounds.

Topics: Animals; Corpus Striatum; Disease Models, Animal; Dizocilpine Maleate; Electromyography; Excitatory Amino Acid Antagonists; Haloperidol; Kynurenic Acid; Parkinson Disease; Quinolones; Rats; Receptors, N-Methyl-D-Aspartate; Reserpine