Interactions of clozapine, thioridazine, and mezilamine with oxotremorine on schedule-controlled responding

The effects of clozapine (0.64-10 mg/kg IM), thioridazine (5-80 mg/kg IM), and mezilamine (0.1-10 mg/kg IM) were determined alone and the presence of 0.05 mg/kg oxotremorine on multiple fixed-ratio, fixed-interval responding in pigeons. All three drugs alone produced a dose-related decrease in responding. Thioridazine and mezilamine produced greater decreases in fixed-interval responding than fixed-ratio responding. Oxotremorine alone decreased responding to 10% of control. Clozapine and thioridazine produced a dose-related antagonism of the behavior-suppressing effects of oxotremorine with 5 mg/kg clozapine completely reversing the behavior-suppressing effects of oxotremorine. In contrast, mezilamine produced no antagonism of the behavior-suppressing effects of oxotremorine. It was concluded that the effects of clozapine on schedule-controlled responding in the pigeon are due to its anticholinergic effects, rather than to its antipsychotic-like effects. Thioridazine also has prominent anticholinergic effects, whereas mezilamine does not have anticholinergic effects.