title: Neurobiological basis of dyskinetic effects induced by antipsychotics: the contribution of animal models.
abstract: Tardive dyskinesia (TD) is a movement disorder characterized by abnormal involuntary facial movements induced by chronic therapy with classical antipsychotic medications. Currently, there is no satisfactory pharmacotherapy for TD, which represents a major limitation to therapy with classical antipsychotics. In order to develop or optimize therapies for TD, and to develop new APDs with lower indices of motor side effects, the pathology underlying TD must first be understood. The use of animal models has been used to further this objective. Here, we review different preparations that have been used to model TD and discuss the contribution of neuroimaging studies conducted in these models. Studies in animal models have lead to several hypotheses of TD pathology, although none has yet emerged as the ultimate underlying cause of this syndrome. We discuss alterations in functional indices, neuron and synapse morphology and changes in specific neurotransmitter systems that have been described in animal models of TD, and outline how these findings have contributed to our understanding of antipsychotic-induced dyskinesias. We conclude that several non-mutually exclusive theories of TD are supported by animal studies, including increases in oxidative stress leading to structural and functional changes in specific neurotransmitter systems. Elucidating the mechanisms underlying TD neuropathology partly through the use of animal models will lead to the development of APDs with superior side effect profiles or more effective therapies for TD.
authors.affiliation: Center for Addiction and Mental Health, Behavioural Neurobiology Laboratory, 250 College Street, Toronto, Ontario M5T 1R8 Canada.
authors.forename: Meaghan C
authors.initials: MC
authors.lastname: Creed
authors.forename: Jose N
authors.initials: JN
authors.lastname: Nobrega
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000473:pathology; D006801:Humans
chemical_list: D014150:Antipsychotic Agents