Subchronic effects of clozapine and haloperidol on rats' forelimb force and duration during a press-while-licking...

In order to compare and contrast the behavioral effects of the typical neuroleptic haloperidol with the atypical neuroleptic clozapine, ten daily doses of these drugs were administered to separate groups of rats trained to extend the forelimb through a rectangular hole and to exert downward pressure on a force transducer to gain access to water. Doses were individually titrated daily for each rat in an attempt to achieve a 50% reduction in time on task (analogous to response rate) during 8-min daily sessions. Clozapine-treated rats exhibited dramatic tolerance to the drug's suppressive effect on time on task. In contrast, haloperidol rats displayed little tolerance on this measure. Despite the tolerance reflected by time on task, no tolerance was seen in clozapine's marked slowing of the dominant frequency of oscillations in forelimb force as measured by Fourier analysis of the force-time recordings. Haloperidol did not slow the dominant frequency. No tolerance was seen for clozapine's effects on forelimb force or tremor measures. Haloperidol did not significantly affect forelimb force. Both haloperidol and clozapine produced increases in the duration of long-duration forelimb responses, and no tolerance was seen for either drug on this measure of behavior. For clozapine, the dissociation between the tendency to respond (time on task) and the observed slowing of the dominant frequency may reflect effects peculiar to atypical neuroleptics, while the lengthening of long-duration responses by both drugs may reflect a more general behavioral effect that is characteristic of both typical and atypical antipsychotic drugs.