Tobacco users are estimated to be at least 1.1 billion worldwide. Although tobacco dependence is not associated with obvious behavioral disruptions, alleviating it is a major public health concern and a main societal challenge, as it produces severe long-lasting health-related problems, leading to 6 million deaths every year. Available therapies for smoking cessation have limited efficacy, warranting the need for developing better therapeutic strategies, which depend on understanding the mechanisms that underlie tobacco dependence, in which nicotine is considered to have a central role.

The relevance of preclinical animal models to nicotine dependence is questioned because their predictive validity is considered poor (Hong et al, 2010). In spite of this, preclinical animal models of nicotine seeking have been proved useful, as they have helped in understanding the mechanisms underlying nicotine seeking. These models, in line with clinical studies, have consistently demonstrated that both pharmacological factors (PF) and non-pharmacological factors (NPF) promote nicotine seeking and have helped identify underlying neurobiological mechanisms (Stoker and Markou, 2015).

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