Can the DRL 72s schedule selectively reveal antidepressant drug activity?

The effects of three antidepressants, desipramine (2.5-20 mg/kg) tranylcypromine (0.63-2.5 mg/kg) mianserin (1.25-10 mg/kg) and three non-antidepressants, chlordiazepoxide (CDP; 1.25-10 mg/kg) haloperidol (0.02-0.16 mg/kg) d-amphetamine (0.31-1.25 mg/kg) were evaluated in rats responding for water reinforcement under a DRL 72s schedule. The antidepressants all produced dose-related decreases in overall response rates, but no significant changes in reinforcement frequency. In contrast, the anxiolytic CDP did increase the number of reinforcers obtained. Haloperidol decreased both reinforcers and responses whilst d-amphetamine stimulated responding, thereby decreasing reinforcement frequency. An analysis of the modes of inter-response times (IRTs) revealed no significant shifts in the peaks of the IRT distributions for most of the drugs tested. Amphetamine, however, (0.31 and 0.63 mg/kg) decreased the modal values in correspondence with the shift to the left of the peak of responding caused by this compound. These results are discussed in the context of the use of the DRL 72s procedure as a screening test for antidepressant drugs.