The effects of reversible inactivation of the subthalamo-pallidal pathway on the behaviour of naive and hemiparkinsonian monkeys

Abstract

This study was designed to further investigate the role of the subthalamic nucleus (STN) and globus pallidus internus (GPi) in the pathophysiology of Parkinson's disease. The prevailing theory about the pathophysiology of Parkinson's disease (PD) predicts that there is overactivity of the subthalamo-pallidal pathway. In order to inactivate that pathway, naive and hemiparkinsonian monkeys were locally administered either muscimol (to reversibly inactivate the contralateral STN) or kynurenic 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. Injection sites of muscimol and kynurenic acid in the brain were confirmed electrophysiologically and histologically. Injections of muscimol into the STN in naive and hemiparkinsonian monkeys caused reversible contralateral dystonia, but did not alleviate Parkinsonism. Only one kynurenic acid injection into GPi partially alleviated Parkinsonism. On the basis of the results in this study, aspects of the currently accepted hypothesis of the pathophysiology of PD cannot be confirmed. However, this study reports that the STN has an important role in the production of dystonia. This experimental model of dystonia will prove suitable for further study of both the mechanisms causing dystonia as well as for possible therapeutic approaches to its treatment.