Pharmacological animal models of Tourette syndrome

Pharmacological animal models of Tourette syndrome (TS) are an important tool for studying the neural mechanisms underlying this disorder. Dysfunction of the cortico-basal ganglia (CBG) system has been widely implicated in TS but the exact nature of this dysfunction is unknown. Pharmacological treatments of TS have prompted multiple hypotheses regarding the involvement of different neuromodulators in the disorder. Pharmacological manipulations in animal models were used to investigate the relationships between these neuromodulators and different symptoms of TS, including motor (tics) and non-motor (sensorimotor gating deficits) phenomena. Models initially focused on the direct effects of pharmacology on behavior, and only recently have begun providing neurophysiological data reflecting the neuronal mechanism linking the two. Animal models support the notion of CBG dysfunction as the neural mechanism underlying TS, and suggest that it may be derived from either direct deficits of local striatal GABAergic networks or a dysfunction of the neuromodulator systems controlling them. These findings can provide the much- needed conceptual construct for the TS etiology and point to new therapeutic targets.