Changes in Striatal N-methyl-D-aspartate (NMDA) Stimulation of Dopamine Release and Receptor Subunit Expression During Expression of and Recovery from MPTP-Induced Parkinsonism

Abstract

Normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated cats were used to examine changes in N-methyl-D-aspartate (NMDA) receptor function. In vivo microdialysis studies showed that NMDA-stimulated dopamine (DA) release was similar in the normal dorso-lateral and ventro-medial caudate nucleus. In symptomatic animals, NMDA-stimulated DA release was significantly decreased in both striatal regions. In symptomatic animals, NMDA-stimulated dopamine release was significantly decreased in both striatal regions. In recovered animals, the dorsal striatum and ventral striatum demonstrated an upregulation in NMDA-stimulated dopamine release compared to symptomatic animals. Receptor autoradiography showed no significant differences in NMDA receptor binding between normal, symptomatic, and recovered animals in the dorso-lateral caudate. NMDA receptor binding was, however, upregulated in the ventro-medial caudate of recovered animals. With Western analysis, NR1 and NR2A subunit levels in the dorso-lateral caudate were shown to decrease significantly in symptomatic animals compared to normal and then increase in recovered animals compared to symptomatic animals. In the ventro-medial caudate, NR1 and NR2A levels in the symptomatic group were significantly increased compared to normal and recovered groups. These data suggest that there may be recovery-induced changes in the functional regulation of the NMDA receptors in the striatum contributing to the behavioral recovery seen in this model.