Blockade ofNMDA receptors differentially affectsD-1 andD-2 mediated turning behavior in the 6-hydroxydopamine model of Parkinson.

In rats with unilateral lesion of the nigrostriatal dopaminergic pathway, L-DOPA induces contralateral turning through activation of denervated D-1 and D-2 receptors. Blockade of N-methyl-D-aspartate (NMDA) receptors by the non-competitive antagonist (+)MK-801, potentiated the contralateral turning induced by L-DOPA as well as that induced by the D-1 agonist SKF 38393, while D-2 mediated turning was almost completely inhibited. Administration of the D-1 antagonist SCH 23390 blocked (+)MK-801-induced potentiation of L-DOPA contralateral turning, confirming the D-1 nature of the effects observed. Immunohistochemical studies on the early gene c-fos, which is known to be activated by stimulation of supersensitive D-1 receptors, revealed sparse c-fos positive nuclei in the lesioned CPu after SKF 38393, while after combined administration of (+)MK-801 and SKF 38393 dense labelling was obtained. Blockade of NMDA receptors, differentially affects D-1 and D-2 mediated turning behavior, suggesting that different neuronal pathways are involved in the mediation of D-1 and D-2 responses.