BACKGROUND An important facet of cocaine addiction is a high propensity to relapse, with increasing research investigating factors that predispose individuals toward uncontrolled drug use and relapse. A personality trait linked to drug addiction is high sensation seeking, i.e., a preference for novel sensations/experiences. In an animal model of sensation seeking, operant novelty seeking predicts the acquisition of drug self-administration. OBJECTIVE The primary goal of this research was to evaluate the hypothesis that sensitivity to the reinforcing effects of novel sensory stimuli predicts more intensive aspects of drug-taking behaviors, such as relapse. METHODS Rats were first tested for Operant Novelty Seeking, during which responses resulted in complex visual/auditory stimuli. Next, rats were trained to respond to water/cocaine reinforcers signaled by a cue light. Finally, rats were exposed to extinction in the absence of discrete cues and subsequently tested in a single session of cue-induced reinstatement, during which active responses resulted in cues previously paired with water/cocaine delivery. RESULTS The present study showed operant responses to produce novel sensory stimuli positively correlate with responding for cocaine during self-administration and during discrete cue-induced reinstatement, but no association with performance during extinction. A different pattern of associations was observed for a natural reward, in this case, water reinforcement. Here, the degree of novelty seeking also correlated with responding to water reinforcement and extinction responding; however, operant novelty seeking did not correlate with responding to water cues during testing of cue-induced reinstatement. Taken together, the incongruence of relationships indicates an underlying difference between natural and drug reinforcers. CONCLUSIONS In summary, we found a reinforcer-dependent relationship between operant novelty seeking (i.e., sensation seeking) and responsivity to extinction and discrete cues signaling availability for cocaine (i.e., craving), demonstrating the validity of the operant novelty seeking model to investigate drug seeking and relapse.