Currently, L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for the motor symptoms in Parkinson's disease (PD). However, long term treatment is associated with several motor complications (e.g. dyskinesia). Clinical improvement of this chronic treatment is therefore needed. Lesions or high frequency stimulation of the subthalamic nucleus (STN), a glutamatergic nucleus which is hyperactive in PD, alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. It has been hypothesized that N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions by reducing the STN-output and/or by altering the glutamatergic input to the STN. However, little is known about the neurochemical changes in the STN induced by co-administration of L-DOPA with a NMDA receptor antagonist.
By means of in vivo microdialysis, the effect of MK801, an NMDA receptor antagonist, on the extracellular dopamine- and glutamate-levels after systemic administration of L-DOPA was investigated in the STN of intact and 6-hydroxydopamine-lesioned rats.
The extracellular dopamine-increase in the STN after L-DOPA administration was significantly higher in hemi-parkinson rats compared to controls. MK801 did not influence the L-DOPA-induced dopamine-release in intact animals. In contrast, MK801 enhanced the L-DOPA-induced dopamine-release in hemi-parkinson rats. The extracellular glutamate-levels in the STN did not alter in both intact and lesioned rats after L-DOPA or L-DOPA/MK801 administration.
This study does not support the hypothesis that MK801 alters the glutamate-levels in the STN. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment of PD by enhancing the therapeutic efficacy of L-DOPA.
Original languageEnglish
Title of host publicationBelgian society for neuroscience biannual meeting 2013
Publication statusPublished - 2013

    Research areas

  • 6-OHDA rat model, Dopamine, Glutamate, Intracerebral microdialysis, L-DOPA, NMDA receptor antagonist, Parkinson's disease, Subthalamic nucleus

ID: 2326454