The effect of novel antipsychotics in rat oral dyskinesia

1. The effect of the D1 agonist SKF38393 and the 5HT(2) C 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 trea ted with both drugs, RJM responses were about equal to the sum of those obt ained with each drug alone. 2. The induction of RJM by SKF38393 was somewhat lower in rats pretreated w ith 5HT(2)C receptor antagonist, mianserin, whereas mianserin severely redu ced 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 opt imal doses for the induction of RJM do not involve the serotonergic system in a significant way. It does, however, implicate the system in the emergen ce of drug induced oral behavior in rats. 5. The effect of the atypical antipsychotics, clozapine, olanzapine and ris peridone was studied on SKF38393 and m-CPP induced RJM. Pretreatment with t he 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.