title: Blockade ofNMDA receptors differentially affectsD-1 andD-2 mediated turning behavior in the 6-hydroxydopamine model of Parkinson.
abstract: 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.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Viale A. Diaz 182, I-09110, Cagliari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morelli
authors.forename: S
authors.initials: S
authors.lastname: Fenu
authors.forename: A
authors.initials: A
authors.lastname: Pinna
authors.forename: A
authors.initials: A
authors.lastname: Cozzolino
authors.forename: G
authors.initials: G
authors.lastname: Di Chiara