Comparison of inhibitory effects of substituted benzamides and classical neuroleptics on operant behavior in rats and squirrel monkeys.

The operant behavioral effects of the substituted benzamides metoclopramide, sultopride and sulpiride were compared with those of chlorpromazine and haloperidol using lateral hypothalamic self-stimulation of the brain in rats and Sidman avoidance responding in rats and squirrel monkeys. All the drugs inhibited both phenomena dose-dependently in rats. The order of potency was: haloperidol greater than chlorpromazine greater than metoclopramide greater than sultopride greater than sulpiride. Sulpiride only produced moderate inhibition even at 128 mg/kg s.c. All drugs also suppressed Sidman avoidance in squirrel monkeys, which were far more sensitive than rats to the inhibitory effects of all three benzamides. In monkeys, sulpiride 8 mg/kg i.m. apparently suppressed Sidman avoidance with a delayed onset and a prolonged duration, which contrasted with the rapid onset and short duration of metoclopramide action. Thus, long-term observation of the behavioral effects of benzamides in squirrel monkeys may provide more precise information on the clinical antipsychotic efficacy of substituted benzamides.