Antidepressant-like effects of (+)-oxaprotiline on a behavioral screen.

(+)-Oxaprotiline (1.25-10 mg/kg), a highly selective and stereospecifically acting norepinephrine (NE) uptake inhibiting drug, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination in rats performing under a differential-reinforcement-of-low-rate 72-s schedule of reinforcement similar to other antidepressant drugs. (-)-Oxaprotiline did not affect the reinforcement rate, response rate or temporal discrimination. Since the most prominent known difference between the oxaprotiline enantiomers is the greater potency for inhibition of norepinephrine (NE) uptake by the (+) enantiomer, the effects of (+)-oxaprotiline in the present studies is probably due to inhibition of NE or epinephrine uptake. The present work also predicts that the therapeutic effects of oxaprotiline in the treatment of affective disorders is due to the (+) enantiomer.