Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function.

Abstract

Evidence indicates that the antipsychotic drug clozapine has a low propensity for the induction of extrapyramidal motor symptoms, and also that clozapine has therapeutic effects in patients with idiopathic Parkinson's disease. Because tacrine-induced tremulous jaw movements in rats have been suggested as a possible model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the present work was undertaken to investigate the effects of clozapine on tremulous jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to determine the relative potency of this effect compared to other behavioral effects of clozapine, suppression of lever pressing was also studied. Clozapine reduced lever pressing in a dose-related manner, with an ED50 of approximately 5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the doses required for suppression of lever pressing. In contrast, the typical antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50 for suppression of lever pressing with that drug. Thioridazine and risperidone also suppressed tremulous jaw movements in roughly the same dose range at which lever pressing was reduced. It is possible that the suppression of tacrine-induced tremulous jaw movements by clozapine in rats is related to the unique behavioral and motor effects of clozapine. The ratio of potencies of these effects (i.e., suppression of tremulous jaw movements versus suppression of lever pressing) could be used as a behavioral procedure for assessing clozapine-like activity in novel compounds.