Clozapine blocks disruptive and discriminative stimulus effects of quipazine.

Clozapine was tested in two serotonin-dependent behavioral measures. One group of rats was trained to discriminate the serotonin agonist, quipazine, from saline in a two-lever operant choice task. Pretreatment with clozapine completely blocked the discrimination of quipazine. Another group of rats was trained to bar press for milk on a variable interval schedule of reinforcement. Quipazine decreased the response rate in these animals and pretreatment with clozapine completely reversed this effect. Thus, clozapine acted as a serotonin antagonist in both measures of serotonin function.