Antidepressants inhibiting the reuptake of both serotonin and norepinephrine may exhibit efficacy superior to that of selective serotonin reuptake inhibitors (SSRIs). Since the clinical effects of antidepressants appear gradually following weeks of treatment, the present study was designed to investigate if there is a benefit to long-term administration of the SSRI, fluoxetine, in comparison with venlafaxine, a 5-HT/norepinephrine (5-HT/NE) reuptake inhibitor (SNRI; both 20 mg/kg ip, once a day for 14 days) in a one-trial step-through passive avoidance task in rats. Locomotor activity was evaluated to assess the effects of the drugs on the motility of the animals. The comparison of training latencies versus test latencies showed inhibition of passive avoidance learning in fluoxetine- or venlafaxine-treated rats (e.g., no significant difference between training and test latencies) in a step-through test. There was no significant difference between fluoxetine- and venlafaxine-induced reduction of latency in rats in this test. Drug Dev. Res. 67:456–461, 2006. © 2006 Wiley-Liss, Inc.