Tardive dyskinesia: pathophysiology and animal models.
Tardive dyskinesia stimulated extensive research into the mechanisms of antipsychotic drug action. A wide range of homologous, analogous, and correlational animal models have been developed to explore how typical neuroleptic drugs do and atypical antipsychotic agents do not seem to cause tardive dyskinesia. The leading hypotheses of the underlying pathophysiology of tardive dyskinesia include dopamine receptor hypersensitivity, GABA insufficiency, and/or structural abnormalities. All these hypotheses have data both for and against them. The roles of psychosis and aging must also be considered in any explanation of tardive dyskinesia. The challenge still remains of how to accurately attribute the relative contributions of each of these factors to the pathogenesis and pathophysiology of tardive dyskinesia. Fortunately, the atypical antipsychotic agents appear to greatly decrease the liability of developing tardive dyskinesia, but how this occurs remains an open and fascinating line of inquiry.
Casey
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Mental Illness Research, Education and Clinical Center, Veterans Affairs Medical Center, Portland, OR 97201, USA. daniel.casey@med.va.gov
D000367:Age Factors; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000033:anatomy & histology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008409:Mastication / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000503:physiopathology; D011618:Psychotic Disorders / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol