Behavioral screen for antidepressants: the effects of drugs and electroconvulsive shock on performance under a differential-reinforcement-of-low-rate schedule.

Those antidepressant drugs that are in wide clinical use decrease response rate and increase reinforcement rate when administered to rats performing on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Drugs that are not antidepressants do not have this effect. In this experiment, the following were examined for their effects on a DRL 72-s schedule: trazodone, zimelidine, fluoxetine, and bupropion (atypical antidepressants); electroconvulsive shock (ECS, which is an effective treatment for depression); and haloperidol and clozapine (antipsychotic drugs). Trazodone (3.12-25.00 mg/kg), fluoxetine (10-20 mg/kg), and ECS decreased response rate and increased reinforcement rate. Zimelidine (20 mg/kg) increased reinforcement rate and nonsignificantly decreased response rate. At doses between 2.5 and 40 mg/kg, bupropion had no effect on reinforcement rate or response rate, but at 60 mg/kg response rate was increased and reinforcement rate was nonsignificantly decreased. At the higher dose, the effects of bupropion resemble those of a psychomotor stimulant. Haloperidol (0.04 mg/kg) and clozapine (2.5-10.0 mg/kg) decreased response rate and reinforcement rate. These results suggest that the DRL 72-s schedule may be useful for testing the antidepressant potential of new drugs.