Nicotine self-administration in animals and humans: similarities and differences.
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.
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