title: Drug-induced oral dyskinesias in rats after traditional and new neuroleptics.
abstract: Tardive dyskinesia (TD) is a serious human side effect of neuroleptic treatment in psychotic disorders. Although the etiology is clear (i.e. chronic neuroleptic drugs), its pathophysiology has not yet been satisfactorily explained. This is important not only theoretically but also to inform drug development, allowing the introduction of antipsychotic compounds without TD liability. The development of an animal condition which putatively models these delayed onset dyskinesias, has provided a technique to differentiate between neuroleptic drug effect and dyskinesia correlates. We report here the development of oral dyskinesias in rats in response to a number of different neuroleptics, which have a range of neurochemical and clinical characteristics. Traditional neuroleptics (e.g. haloperidol) produced rat oral dyskinesias, in an open-cage environment. Clozapine, while it produced an increased rate of oral movements, showed a significantly decreased potency in this model. SCH23390 (D1 antagonist) neither produced the oral movements nor modified their onset by coadministration with raclopride. These data replicate and extend other similar studies in the literature. They suggest that clozapine differs from traditional neuroleptics with respect to motor side effects.
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kakigi
authors.forename: X M
authors.initials: XM
authors.lastname: Gao
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D004327:Drinking Behavior / Q000187:drug effects; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology / Q000523:psychology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents