INTRANIGRAL BUT NOT INTRASTRIATAL MICROINJECTION OF THE NMDA ANTAGONIST MK-801 INDUCES CONTRALATERAL CIRCLING IN THE 6-OHDA RAT MODEL

When systemically administered to unilaterally 6-OHDA lesioned rats, the non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] 5,10-imine) produces a marked rotation response toward the lesioned side. In addition, the same type of injection in non-denervated rats increases locomotor activity without direction predominance. These findings suggest that MK-801 interacts with the dopaminergic pathway to induce motor activity. However, intracerebral injection of MK-801 (5 mu g/0.5 mu l) in the substantia nigra pars reticulata (SNr), either on the lesioned side or the intact side, induces a significant circling response, contraversive to the injection side. A similar injection of MK-801 (5 mu g/1.0 mu l) in the striatum causes no rotation response. These results show that the non-competitive NMDA antagonist can induce motor activity in the presence or in the absence of the dopaminergic pathway and that in the latter case its action is exerted predominantly at the level of the substantia nigra, perhaps through suppression of the excitatory subthalamic drive.