Relevance of animal models to human tardive dyskinesia

Abstract

Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.

Figure 1

Seven capuchins displaying tardive dyskinetic movements causing variable tongue protrusions, as well as forehead contractions, lip retraction, and neck twisting.

Figure 2

Mean (± SD) tardive dyskinesia scores obtained in 6 animals rated on 3 different occasions 4 weeks apart. Individual scores represent the sum of several body parts. The mean coefficient of variation calculated from this data set with normal distribution is 31.5%.