Chapter M3 - Motor Effects of Typical and Atypical Antipsychotic Drugs in Rodents

Abstract

Typical antipsychotic drugs (APDs) induce use-limiting extrapyramidal side effects (EPS) that resemble the motor manifestations of Parkinson's disease. Although the newer atypical antipsychotic drugs produce less EPS than typical APDs, these newer drugs, nevertheless, produce a variety of motor effects. This chapter provides an overview of studies that used force-transducer technology in two different experimental paradigms to characterize the low-dose motor effects of both typical and atypical APDs in rats. In a paradigm that afforded measures of tongue dynamics, acute doses of the atypical APDs, clozapine, risperidone, and Olanzapine, were shown to slow lick rhythm, while acute doses of the typical APD haloperidol and the selective D2 antagonist raclopride produced much less effect on the rhythm of tongue movements during licking. The fact that clozapine's profile of motor effects in rats is paralleled by similar tremor-reducing and force-control effects in human patients suggests that the methods of assessing motor behavior in the rats may be useful in research designed to identify APDs with clozapine-like effects. Clozapine appears to have unique effects on motor behavior, and this distinctive behavioral profile may hasten the search for compounds with similar effects.