Dyskinesia: animal experimental correlates.

The results of behavioral studies in animals, which demonstrate increased effects of DA agonists after stopping chronic administration of neuroleptics, are consistent with an increased sensitivity of postsynaptic receptor and effector mechanisms in response to chronic disruption of DA transmission (disuse supersensitivity of DA receptors, see review by Moore & Thornburg (1975)). Although this mechanism may be responsible for the reversible withdrawal dyskinesias, it is probably not involved in persistent tardive dyskinesia. The persistence of the latter dyskinesias suggests an irreversible structural or chemical change, but with the exception of a report by Christensen et al. (1970) there is little evidence of neuroleptic-induced degenerative changes in the brains of man or animals. Although the etiology of tardive dyskinesias remains a mystery, pharmacological evidence suggests a functional overactivity of extrapyramidal mechanisms mediated by DA. To date, however, experiments with animal models have not provided a logical explanation for this overactivity.