Blockade of subthalamic glutamatergic activity corrects changes in neuronal metabolism and motor behavior in rats with nigrostriatal lesions

We infused-for four weeks-a selective antagonist of the NMDA receptor, MK-8 01, into the subthalamic nucleus of rats bearing an evolving nigrostriatal lesion. The aim was to block the subthalamic overactivity resulting from th e dopaminergic striatal denervation. The nigrostriatal lesion caused metabo lic activation-increased activity of the mitochondrial enzyme succinate deh ydrogenase-of basal ganglia nuclei, ipsilaterally to the lesion, along with contralateral rotational behavior. These phenomena were effectively counte racted by the blockade of glutamatergic transmission at the subthalamic lev el. Pharmacological manipulation of the STN, through selective drugs capabl e of modulating glutamatergic transmission, may therefore represent a valua ble tool for the treatment of PD.