title: Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.
abstract: A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction.
  
  
  CONCLUSIONS
  This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of preclinical research for research questions related to nicotine reduction.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA.|Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Smith
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.affiliation: Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Denlinger-Apte
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA.
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Weeks
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Panas
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA.|Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D011634:Public Health; D012107:Research Design; D012646:Self Administration; D014029:Tobacco Use Disorder
chemical_list: D009538:Nicotine