ABSTRACT: In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1 mg/kg/infusion, delivered over different durations (1.8 or 100 s). Two groups were trained with either short or long infusions paired with a visual stimulus change (lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-s infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-s infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. RESEARCH HIGHLIGHTS: ▸ In this study we examined the effects of infusion duration on cocaine self-administration in rats. ▸ We found that when a stimulus was associated with the cocaine infusion, infusion duration had little effect on the acquisition of cocaine self-administration. ▸ When no stimulus was associated with the cocaine infusion, cocaine self-administration was acquired only with the faster cocaine infusion. ▸ These results indicate that infusing a given dose of cocaine more rapidly reduces its ability to support self-administration, but drug-paired stimuli can mask this effect by enhancing the effectiveness of slow infusions.