Original Investigation


, Volume 226, Issue 3, pp 551-560

First online:

The effect of previous exposure to nicotine on nicotine place preference

  • Verónica PastorAffiliated withDepartment of Physiology and Institute of Cell Biology, School of Medicine, University of Buenos Aires
  • , María Estela AndrésAffiliated withDepartment of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile
  • , Ramón O. BernabeuAffiliated withDepartment of Physiology and Institute of Cell Biology, School of Medicine, University of Buenos Aires Email author 

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Prior exposure to drugs of abuse may increase or decrease the reinforcing effects of the drug in later consumptions. Based on the initial locomotor activity (LA) response to an acute drug administration or to novelty in an open-field arena, animals can be classified as low or high LA responders (LR or HR). Few studies have used this classification with nicotine, and the results are controversial. Some authors suggested that nicotine can induce conditioned-place preference (CPP) following prior nicotine exposure, whereas others suggested that previous nicotine exposure extinguishes nicotine-CPP.


To explore if the administration of nicotine in a novel environment without explicit behavioral consequences to classify animals in low and high nicotine responders (LNR and HNR) could affect the establishment of nicotine CPP in male Sprague–Dawley rats.


Prior exposure to a single dose of nicotine (0.4 mg/kg, subcutaneously) induced CPP in LNR rats after 14 days of conditioning (seven-trial) but not after two or eight conditioning days. In contrast, HNR rats did not show CPP under any condition. In addition, our results indicated that previous exposure to nicotine decreased its rewarding effects in eight conditioning days CPP (four-trial), which can be regularly established without prior exposure to nicotine.


The results suggested that response to a single exposure to nicotine predicts the acquisition of nicotine preference in a 14-day conditioning protocol only for LNR rats. Thus, our findings demonstrated the relevance of using LNR and HNR classification when the individual susceptibility to nicotine preference is studied.


Nicotine Conditioned-place preference Low and high locomotor activity responders