Effects of clozapine and chlorpromazine upon operant response measures in rats

Rats responded under a FR20 schedule of water reinforcement by paw-pressing a silent, isometric, force-sensing manipulandum. Two seven-animal groups differed in terms of the force requirement for reinforcer delivery, i.e., a low-force condition (4-g requirement for reinforcer delivery) or a high-force condition (32-g requirement for reinforcer delivery). Oral dose ranges of chlorpromazine (1.0, 3.0, 9.0 mg/kg) and clozapine (2.5, 5.0, 10.0 mg/kg) were evaluated for their effects on intensitive measures of response (i.e., peak force and duration), in addition to the conventional rate measure. Peak force, duration, and rate of response were recorded with a laboratory computer system. Conjoint examination of these three dependent variables revealed that clozapine, a new anti-psychotic agent which produces virtially no extrapyramidal side effects in man, affected FR responding in the same way as did chlorpromazine. More specifically, response rate and peak force declined as a function of dose for each drug. Duration of response tended to be increased at the highest dose for both clozapine and chlorpromazine, but this effect was limited primarily to the high-force condition.