TURNING BEHAVIOR INDUCED BY INJECTIONS OF GLUTAMATE-RECEPTOR ANTAGONISTS INTO THE SUBSTANTIA-NIGRA OF THE RAT

We have found recently that muscimol microinjections into the subthala mic nucleus produce contralateral turning activity [Murer and Pazo (19 93) NeuroReport, 4:1219-1222]. To test the hypothesis that a reduced g lutamate action on substantia nigra pars reticulata neurons mediates t his turning response, we examined the effect of unilateral intranigral microinjections of the AMPA/kainate receptor antagonist 6,7-dinitro-q uinoxaline-2 ,3-dione (DNQX) and the competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5). DNQX and AP-5 both produced a dose-dependent contralateral turning res ponse, while vehicle administration did not induce turning activity. A pplication of glutamate receptor antagonists at adjacent regions of th e mesencephalic tegmentum were also ineffective. Coadministration of N MDA or AMPA significantly reduced the turning response induced by AP-5 or DNQX, respectively. Lesions of the nigrostriatal pathway by 6-hydr oxydopamine did not modify the response to DNQX or AP-5 administration into the nigra. However, their behavioral effects were significantly reduced by a lesion of the ipsilateral subthalamic nucleus. Our result s show that the blockade of a tonic input acting on AMPA/kainate and N MDA receptors located at the substantia nigra produces contralateral t urning behavior. The effect seems to involve pars reticulata cells sin ce this area remains unchanged after destruction of dopaminergic neuro ns. The subthalamic nucleus seems to be the endogenous source of the a gonist acting on the nigral glutamate receptors related to turning beh avior. (C) 1996 Wiley-Liss, Inc.