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Cocaine inhibits the reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). To investigate the relative role of such reuptake processes in the discriminative stimulus properties of cocaine, male rats (N=16) were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced drug discrimination task and were administered neuroactive compounds during substitution or combination tests. The DA reuptake inhibitor GBR 12909 (2–16 mg/kg) completely mimicked cocaine. The reuptake inhibitors for NE (desipramine; 2–8 mg/kg) and 5-HT (fluoxetine; 0.625–5 mg/kg) did not substitute for the training drug. A low dose of either desipramine (3 mg/kg), fluoxetine (1.25 mg/kg), or GBR 12909 (2 mg/kg) coadministered with low doses of cocaine (0.625–2.5 mg/kg) enhanced the discriminative stimulus properties of this psychostimulant. The dose predicted to elicit 50% drug-lever …