<p>[Introduction] Despite the health damage risks of tobacco, success rate of smoking cessation is quite low. Tobacco dependence has aspects of substance and behavioral addiction. The latter aspect is supported by the limited efficacy of smoking cessation by nicotine replacement therapy such as nicotine gum or patches. In this study, to clarify the mechanism of behavioral addiction with smoking, we established the model of nicotine intake behaviors in mice corresponding to behavioral addition in human smokers, and examined the brain region associated with nicotine intake behaviors. [Methods] Two drinking bottles were placed on the housing cage of mice (C57BL/6J, 8-9 weeks, male). After the habituation period, mice were exposed to the water containing nicotine (75µg/ml) filled in both bottles for one week to learn nicotine intake behavior (behavioral priming). Then, to measure the preference to nicotinic solution, bottles containing vehicle or nicotinic solution were presented to mice. [Results] Mice which experienced behavioral priming much more preferred to the nicotinic solution than those without behavioral priming. Immunohistochemistry to FosB, a marker of neuronal activity, revealed that larger number of FosB-positive neurons were observed in the basolateral amygdala (BLA) in mice without the preference to the nicotine solution, than those with preference. [Conclusion] Enhanced neuronal activity in the BLA is suggested to be associated with behavioral addiction of tobacco dependence.</p>