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Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis


The movement disorder tardive dyskinesia is a serious side effect of the long-term treatment of schizophrenia with neuroleptic drugs. Similar symptoms to those of tardive dyskinesia have been observed in Cebus apella monkeys following long-term treatment with neuroleptic drugs1,2, and these monkeys may therefore be a useful animal model of tardive dyskinesia. Motor defects have persisted in these dyskinetic monkeys for periods of 1–6 yr after the cessation of neuroleptic treatment. We report here that in three regions of the brains of dyskinetic monkeys (substantia nigra, medial globus pallidus and subthalamic nucleus) glutamate decarboxylase activities and γ-aminobutyric acid (GABA) levels are reduced relative to control monkeys that had been treated with neuroleptics but which showed none of the symptoms of tardive dyskinesia. These results suggest that alterations in the GABA neurone system are involved in neuroleptic drug-induced tardive dyskinesia.

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Gunne, LM., Häggström, JE. & Sjöquist, B. Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. Nature 309, 347–349 (1984).

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