Experimental tardive dyskinesia.

Abstract

In this work, we have attempted to reproduce dyskinesia similar to tardive dyskinesia by two methods. In the first experiment, we have administered to 6 macaca mulatta, haloperidol 0.25 mg/kg daily for six months. During that period we observed in all monkeys, after each dose: restlessness, akinesia and tremor. One monkey developed choreoathetoid movements, which were seen each day after the first month. They disappeared however upon cessation of the drug administration. Only one animal developed a bucco lingual dyskinesia after two months which was still present when they were sacrificed six month after the drug administration was discontinued. At that time, harmaline 3 mg/kg induced a postural tremor in all monkeys suggesting a lesion of the rubro-olivo-cerebello rubral loop. Histological analysis of the brains revealed no gross abnormality. In a second experiment, a left midbrain electrolytic lesion was performed in twelve monkeys. One monkey, developed a contralateral tremor but five including the trembling one developed a buccolingual dyskinesia which has now lasted more than a year. This dyskinesia is present at rest but increased by dopaminergic agents and blocked by haloperidol. Histological analysis of the brain of one of the monkeys revealed a dorsal lesion involving the region of the nucleus parafascicularis thalami. The substantia nigra was spared.