Preclinical models relevant to Tourette syndrome.

Abstract

Preclinical models, if used appropriately, can greatly accelerate the understanding of neuropsychiatric disorders. A number of animal models have predictive validity for antidopaminergic compounds that have traditionally been used to suppress motor and vocal tics in TS. Other models have been proposed that may have construct validity for specific hypotheses of infectious/immune and neural circuit etiologies of TS. A more comprehensive set of models is described, based on the hypothesis that primary symptoms of TS, including sensory tics and premonitory urges, result from dysfunction in brain mechanisms that regulate sensorimotor gating. These models utilize operational measures of central gating mechanisms, including PPI of the startle reflex, to achieve predictive validity across a number of different chemical classes of drugs, and to achieve construct validity across broad domains of neurodevelopmental, immune and genetic etiologies of TS. PPI-based animal models offer a number of strong advantages for predictive and mechanistic studies of TS. Ultimately, the utility of these "deficient gating" models will be judged by their ability to bring us closer to identifying the causes and effective treatments of this disorder.