The drug discrimination paradigm was used to evaluate in rats the ability of the discriminate response to either 0.8 mg/kg d-amphetamine or 0.8 mg/kg l-cathinone to generalize to 2.4-6.0 mg/kg of the active cathinone metabolite d-norpseudoephedrine, also known as cathine. When tested 24 h after vehicle administration, cathine generalized in a dose-related fashion in rats (n = 6) trained with cathinone (ED50 = 3.03 mg/kg) and in rats (n = 8) trained with amphetamine (ED50 = 2.93 mg/kg). In contrast, when cathine was tested 24 h after the administration of either amphetamine or cathinone, it produced significantly decreased discriminative performance. The possibility that this acute tolerance may have been produced by release, and subsequent depletion, of brain dopamine was tested by pretreating rats with the dopamine release inhibitor CGS 10746B. When CGS 10746B was administered prior to cathinone it significantly decreased cathinone discrimination. In addition, acute tolerance to cathine at 24 h after vehicle-cathinone co-administration was reversed when cathine was tested 24 h after CGS 10746B-cathinone co-administration. The results suggest that cathinone-produced discriminative stimulus, as well as the acute tolerance to cathine, may be dopaminergically mediated.