Reorganization of basal ganglia circuitry in animal model of parkinson's disease by stimulation of subthalamic nucleus

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To test the hypothesis that STN-DBS inducesa long-lasting reconstruction of basal gangliacircuitry in parkinsonian rats mediatedby expression of LTP on synapses in the nearby nuclei, we examined whether NMDA receptor(NMDAR) subunit NR2B antagonist potentiates the alleviating after-effect of STN-DBS and lasts the improvement of motor deficits by transient STN-DBS long for hours or days.Prior to the test for the potentiation of alleviating effect of STN-DBS by NR2B antagonist in hemi-parkinsonian rats, we first examined whether mono-therapeutic treatment with NR2B antagonist(ifenprodil) improves the motor symptoms in hemi-parkinsonian rats. As a result, in hemiparkinsonianrats, we found that ifenprodil did not cause an improvement of the deficits of motor coordination, while the drug potentiated the ameliorative effect of L-DOPAon the deficit of motor coordination whencombined with L-DOPA, suggesting the synergistic action of ifenprodil on the antiparkinsonian effect of L-DOPA. From this result, it is suggested that a combined treatment with STN-DBS and NR2B antagonist could be more effective than STN-DBS alone to improve the chronic L-DOPA-induced dyskinesias with less side-effect.