THE EFFECTS OF REVERSIBLE INACTIVATION OF THE SUBTHALAMOPALLIDAL PATHWAY ON THE BEHAVIOR OF NAIVE AND HEMIPARKINSONIAN MONKEYS

This study was designed to further investigate the role of the subthal amic nucleus (STN) and globus pallidus internus (GPI) in the pathophys iology of Parkinson's disease. The prevailing theory about the pathoph ysiology of Parkinson's disease (PD) predicts that there is overactivi ty of the subthalamo-pallidal pathway. In order to inactivate that pat hway naive and hemiparkinsonian monkeys were locally administered eith er muscimol (to reversibly inactivate the contralateral STN) or kynure nic acid (to reduce glutamatergic activity in the contralateral GPi). Three naive and 2 hemiparkinsonian monkeys were studied. Intra-carotid MPTP was administered to produce 2 hemiparkinsonian monkeys. injectio n sites of muscimol and kynurenic acid in the brain were confirmed ele ctrophysiologically and histologically. injections of muscimol into th e STN in naive and hemiparkinsonian monkeys caused reversible contrala teral dystonia, but did not alleviate Parkinsonism. Only one kynuremic acid injection into GPi partially alleviated Parkinsonism. On the bas is of the results in this study, aspects of the currently accepted hyp othesis of the pathophysiology of PD cannot be confirmed. However, thi s study reports that the STN has an important role in the production o f dystonia. This experimental model of dystonia will prove suitable fo r further study of both the mechanisms causing dystonia as well as for possible therapeutic approaches to its treatment.