Tardive dyskinesia: Pathophysiology and animal models

Tardive dyskinesia stimulated extensive research into the mechanisms of ant ipsychotic drug action. A wide range of homologous, analogous, and correlat ional animal models have been developed to explore how typical neuroleptic drugs do and atypical antipsychotic agents do not seem to cause tardive dys kinesia. The leading hypotheses of the underlying pathophysiology of tardiv e dyskinesia include dopamine receptor hypersensitivity, GABA insufficiency , and/or structural abnormalities. All these hypotheses have data both for and against them. The roles of psychosis and aging must also be considered in any explanation of tardive dyskinesia. The challenge still remains of ho w to accurately attribute the relative contributions of each of these facto rs to the pathogenesis and pathophysiology of tardive dyskinesia. Fortunate ly, the atypical antipsychotic agents appear to greatly decrease the liabil ity of developing tardive dyskinesia, but how this occurs remains an open a nd fascinating line of inquiry.