Electrophysiological Study of Dyskinesia Produced by Microinjection of Picrotoxin into the Striatum of the Rat

Abstract

From the findings in human diseases, such as the main pathological change in Huntington’s disease is an atrophy of caudate neurons, striatum has been related to dyskinesia. It was, however, difficult to produce an animal model of dyskinesia by electrostimulation or lesioning of the striatum. In the 1970’s, by pharmacological manipulation of the striatum, a model of dyskinesia was reported; that is, injection of picrotoxin (PTX), a selective antagonist of γ-aminobutyric acid (GABA), into the striatum of the rat and cat produced dyskinesia similar to choreiform or myoclonic movements (McKenzie and Viik, 1975; Tarsy et al., 1978). The underlying neuronal mechanism of the dyskinesia, however, is not yet fully understood. In this paper, we performed the following experiments to define more precisely the nature of the dyskinesia and to elucidate the underlying neuronal mechanism. 1) We studied behaviorally the influence of the dopaminergic system on the dyskinesia, since dopamine is closely related to choreiform dyskinesia as L-DOPA induced dyskinesia. 2) We investigated electrophysiologically changes in neuronal activities in the striatum and its output structures during dyskinesia.