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Guidelines on nicotine dose selection for in vivo research

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Abstract

Rationale

This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure.

Objectives

This review capitalizes on the authors’ collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models.

Results

Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses.

Conclusions

The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose–response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.

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Acknowledgements

The conceptualization of this review grew out of discussions among the Nicotine Dependence Study Section members who review grant applications for the Tobacco-related Disease Research Program (TRPRP), University of California Office of the President. In addition, TRDRP supported the discussion meetings, compilation, and writing of this review. Although it is customary to acknowledge all funding sources, it simply is not feasible here, given the number of contributors to this review and the extensive, ongoing support by multiple institutions; acknowledgement of specific individual support is provided in each author’s primary papers in the references. Finally, with the exception of the first author/editor, authorship is listed alphabetically.

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Matta, S.G., Balfour, D.J., Benowitz, N.L. et al. Guidelines on nicotine dose selection for in vivo research. Psychopharmacology 190, 269–319 (2007). https://doi.org/10.1007/s00213-006-0441-0

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