The effects of clozapine on shuttle-box avoidance responding in rats: comparisons with haloperidol and chlordiazepoxide.

Previous studies have shown that clozapine produces effects different from those of other antipsychotic drugs on positively reinforced responding but may give rise to similar disruptions of avoidance behavior. To investigate the actions of clozapine on avoidance responding in more detail the effects of this drug were compared with those of haloperidol and chlordiazepoxide in rats trained to avoid shock in a shuttle-box. Acute administration of all three drugs reduced avoidance responses and increased escape failures although clozapine produced this latter effect only at a high dose. With repeated administration of each drug over 4 days tolerance developed rapidly to the effect of clozapine, the effect of haloperidol increased and there was no systematic change in the action of chlordiazepoxide. Disrupted avoidance responding after acute administration of clozapine does not reflect the clinical antipsychotic action of this drug.