The effect of novel antipsychotics in rat oral dyskinesia

1. The effect of the D1 agonist SKF38393 and the 5HT2C agonist m-CPP on repetitive jaw movements (RJM) was studied in rats. Acute administration of SKF38393 and/or m-CPP induced RJM in a dose dependent manner. In rats treated with both drugs, RJM responses were about equal to the sum of those obtained with each drug alone. 2. The induction of RJM by SKF38393 was somewhat lower in rats pretreated with 5HT2C receptor antagonist, mianserin, whereas mianserin severely reduced RJM induced by m-CPP alone. 3. D1 antagonist SCH23390 inhibited SKF38393 induced RJM but had no effect on m-CPP induced chewing behavior. 4. The present study confirms earlier evidence that D1 agonists used at optimal doses for the induction of RJM do not involve the serotonergic system in a significant way. It does, however, implicate the system in the emergence of drug induced oral behavior in rats. 5. The effect of the atypical antipsychotics, clozapine, olanzapine and risperidone was studied on SKF38393 and m-CPP induced RJM. Pretreatment with the atypical antipsychotics clozapine and olanzapine inhibit SKF38393 and m-CPP induced RJM. Pretreatment with risperidone inhibits m-CPP induced oral behavior in rats while increases dose dependently SKF38393 induced RJM.