The NR2B antagonist, ifenprodil, corrects the l-DOPA-induced deficit of bilateral movement and reduces c-Fos expression in the subthalamic nucleus of hemiparkinsonian rats

•Antiparkinsonian effect of ifenprodil in PD rats was tested using cylinder test.•l-DOPA improved akinesia, but bilateral forelimb use was not recovered.•Single administration of ifenprodil did not show antiparkinsonian effects.•Co-administration of ifenprodil and l-DOPA improved bilateral forelimb use.•Administration of ifenprodil suppressed l-DOPA-induced c-Fos expression in the STN.

The use of NR2B antagonists in Parkinsonism is still controversial. To examine their anti-parkinsonian effects, the NR2B antagonist, ifenprodil, and l-DOPA were administered together and separately in hemiparkinsonian rats (hemi-PD) that were subjected to a cylinder test. Recovery from hypoactivity was achieved by single administration of 3-7 mg/kg of l-DOPA; however, improvement in the deficit of bilateral forelimb use was not observed. When administered alone, ifenprodil had no anti-parkinsonian effects; however, combined administration of ifenprodil and 7 mg/kg of l-DOPA significantly reversed the deficit of bilateral forelimb use without adversely affecting the l-DOPA-induced improvement in motor activity. Next, in order to identify the brain area influenced by l-DOPA and ifenprodil, quantitative analysis of l-DOPA-induced c-Fos immunoreactivity was performed in various brain areas of hemi-PD following administration of l-DOPA with and without ifenprodil. Among brain areas with robust c-Fos expression within the motor loop circuit in dopamine-depleted hemispheres, co-administered ifenprodil markedly attenuated l-DOPA-induced c-Fos expression in only the subthalamic nucleus (STN), suggesting that the STN is the primary target for the anti-parkinsonian action of NR2B antagonists.