CHRONIC OLANZAPINE OR SERTINDOLE TREATMENT RESULTS IN REDUCED ORAL CHEWING MOVEMENTS IN RATS COMPARED TO HALOPERIDOL

Chronic haloperidol treatment typically produces late-onset, purposele ss oral chewing movements in laboratory mts with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewi ng movements and human tardive dyskinesia (TD), the animal movements a re often used as a model of tardive dyskinesia (TD). Here we report re sults of the association of oral chewing movements in rats with chroni c administration of two new antipsychotic drugs, olanzapine and sertin dole. Because each of these antipsychotic drugs has a very low inciden ce of acute Parkinsonism in human studies, they are candidates for sho wing a low tardive dyskinesia risk. Neither new drug produced a signif icant incidence of haloperidol-like chewing in rats, nor did movement ratings after their chronic administration differ from placebo; wherea s, haloperidol produced a 60% prevalence of purposeless chewing and a prevalence significantly increased from placebo. This low rate of oral dyskinesias in mts is consistent with several of the preclinical char acteristics of the drugs and correlates with their low acute motor sid e effects in clinical trials. We propose, although have not yet tested in humans, that these animal results will predict low TD liability Of these drugs. [Neuropsychopharmacology 19:428-433, 1998] (C) 1998 Amer ican College of Neuropsychopharmacology. Published by Elsevier Science Inc.