Studies of
nicotine self-administration in animal and human subjects are discussed with respect to the behavioral paradigms employed, the effects of
nicotine dose manipulations and
nicotinic agonist/antagonist pretreatment, and the role of neurochemical processes mediating reinforcement. Animal models have focused on intravenous
nicotine self-administration, while most studies in human subjects have studied cigarette smoking behavior. Despite procedural differences, data from both animal and human studies show an inverted-U function relating
nicotine dose to
self-administration behavior, with maximal rates of responding occurring at intermediate doses of
nicotine. Moreover,
nicotine supplementation via non-contingent
nicotine administration suppresses
nicotine self-administration behavior in both animal models and human cigarette smokers.
Nicotine antagonist treatment also reduces responding, although human studies usually find a transient increase in smoking, which is interpreted as an attempt to compensate for
nicotinic receptor blockade. Amongst the neurochemical systems which have been examined, most emphasis has been given to
dopamine. The mesolimbic
dopamine pathway has been implicated in
nicotine reward based on animal studies, and research with humans suggests a role for dopaminergic processes as well. However, dopaminergic blockade appears to increase cigarette smoking behavior in humans, while in animals
nicotine self-administration is attenuated. Future research should exploit the complementary aspects of animal models and human paradigms to provide a coherent understanding of
nicotine reinforcement. Animal models allow for analysis of anatomical and physiological mechanisms underlying
nicotine self-administration; human studies validate the relevance to
tobacco dependence and smoking cessation treatment.