Tardive Dyskinesia: Pathophysiology and Animal Models

Tardive dyskinesia stimulated extensive research into the mechanisms of antipsychotic drug action.A wide range of homologous, analogous, and correlational animal models have been developedto explore how typical neuroleptic drugs do and atypical antipsychotic agents do not seem to causetardive dyskinesia. The leading hypotheses of the underlying pathophysiology of tardive dyskinesiainclude dopamine receptor hypersensitivity, GABA insufficiency, and/or structural abnormalities. Allthese hypotheses have data both for and against them. The roles of psychosis and aging must also beconsidered in any explanation of tardive dyskinesia. The challenge still remains of how to accuratelyattribute the relative contributions of each of these factors to the pathogenesis and pathophysiologyof tardive dyskinesia. Fortunately, the atypical antipsychotic agents appear to greatly decrease theliability of developing tardive dyskinesia, but how this occurs remains an open and fascinating line ofinquiry.