MK801 influences l-DOPA-induced dopamine release in intact and hemi-parkinson rats

Abstract

In vivo microdialysis was used to investigate the influence of dizocilpine (MK801) on basal and levodopa ( l-DOPA)-induced extracellular dopamine levels in striatum and substantia nigra of intact and 6-hydroxydopamine-lesioned rats. In lesioned rats, extracellular dopamine was decreased in striatum but not in substantia nigra. l-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) increased the dopamine levels in striatum and substantia nigra of intact and dopamine-depleted rats. This increase was significantly higher in dopamine-depleted compared to intact striatum. Pretreatment with MK801 (0.1 and 1.0 mg/kg i.p.) dose-dependently attenuated the l-DOPA-induced dopamine release in substantia nigra of intact rats. In dopamine-depleted striatum, MK801 enhanced l-DOPA-induced dopamine release. The present results indicate that the influence of MK801 on l-DOPA-induced dopamine release in striatum and substantia nigra depends on the integrity of the nigrostriatal pathway. In Parkinson's disease, NMDA receptor antagonists could be beneficial by enhancing the therapeutic efficacy of l-DOPA at the level of the striatum.