Pharmacological animal models of tic disorders

This review summarizes animal models of Tourette syndrome (TS) and associated tic disorders that have been developed through pharmacological manipulation. These models provide a useful platform to explore the pathophysiology and the therapeutic interventions available for these disorders. The current pharmacological models, primarily using rodents and nonhuman primates, are classified in this review into two major categories depending on the methodology used for administration, that is, systemic and focal (intracerebral) injection protocols. The systemic protocol primarily targets monoamines such as dopamine and serotonin, whereas the focal protocol mainly manipulates local transmission of gamma-aminobutyric acid (GABA). Each category is capable of inducing behavioral abnormalities that are characteristic of TS spectrum disorders, ranging from sensorimotor to cognitive and emotional symptoms to various degrees. Among a variety of pharmacological models, focal microinjection of GABA antagonists into the sensorimotor striatum has helped identify abnormal neural discharge in the global networks which underlie tourettism, including not only the cerebral cortex and basal ganglia but also the cerebellum, consistent with recent neuroimaging studies for TS subjects. This unique model also provides the opportunity to clarify the effect and mechanisms of therapeutic deep brain stimulation. Continuing efforts to incorporate cutting-edge knowledge into the existing models, as well as to combine different model platforms, will allow further refinement of animal models, thereby leading to a greater understanding of TS and associated tic disorders.