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Rationale Prolonged use of nicotine appears to enhance incentive salience, a motivational-cognitive process that transforms an otherwise neutral stimulus into a Bwanted stimulus. It has been suggested that nicotinic enhancement of incentive salience contributes to the potential of relapse in individuals with tobacco addiction. However, there are two main limitations of prior research that caution this claim: (a) the use of passive experimentally delivered nicotine and (b) the use of sign-tracking as an index of incentive salience, without acknowledging the competing nature of goal- and sign-tracking responses. Objectives To determine whether nicotinic enhancement of incentive salience attributed to non-nicotinic stimuli occurs when rats self-administer nicotine, and whether it is facilitated by a prior history of nicotine self-administration. Methods Twenty-three male rats were trained daily, for 24 days, on a nicotine self-administration (SA) paradigm in the morning, and on a four-conditioned-stimuli Pavlovian conditioned approach (4-CS PCA) task in the afternoon. Self-administration was followed by extinction and cue reinstatement. A subcutaneous nicotine challenge was performed during the last 7 days of the study. Results Nicotine self-administration selectively enhanced sign-tracking in the 4-CS PCA. Upon extinction, sign-tracking quickly declined to control levels. Experimenter-administered nicotine enhanced sign-tracking similarly regardless of nicotine history. Conclusions The results suggest that nicotinic enhancement of incentive salience is transient, and a previous history of nicotine use does not cause further sensitization. Taken together, these results suggest that nicotine enhances incentive salience, particularly-- and perhaps exclusively--while onboard. [ABSTRACT FROM AUTHOR]