Effects of glutamate and MK-801 on the metabolism of dopamine in the striatum of normal and parkinsonian rats.

The direct effects of glutamate and dizocilpine maleate (MK-801, non-competitive N-Methyl-D-aspartate glutamate receptor antagonist) on the metabolism of dopamine were investigated in the striatum of normal and parkinsonian rats. L-dopa, L-glutamic acid and MK-801 were administered in the striatum locally by microdialysis. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were simultaneously sampled by microdialysis. The concentrations of DOPAC and HVA were assayed by high performance liquid chromatography with electrochemical detection (HPLC-ECD). L-dopa increased the concentrations of DOPAC and HVA in the striatum of normal and parkinsonian rats. L-glutamic acid decreased the concentrations of DOPAC and HVA in striatum of normal rats but not parkinsonian rats. MK-801 increased the concentrations of DOPAC and HVA in the striatum of normal rats but not parkinsonian rats. MK-801 prevented the L-glutamic acid-induced decrease of DOPAC and HVA in the striatum of normal rats. Our results indicate that glutamate modulates the metabolism of dopamine (DA) through NMDA receptors and that the improvement of PD by MK-801 is not through improving the metabolism of DA.