Guidelines on nicotine dose selection for in vivo research

Abstract

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. 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. 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. 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.

DOI: 10.1007/s00213-006-0441-0

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@article{Matta2006GuidelinesON, title={Guidelines on nicotine dose selection for in vivo research}, author={Shannon G. Matta and David J. K. Balfour and Neal L. Benowitz and Robert Boyd and Jerry J . Buccafusco and Anthony R. Caggiula and Caroline R. Craig and Allan C. Collins and Mohamad Imad Damaj and Eric C. Donny and Phillip S. Gardiner and Sharon R. Grady and Ulrike A Heberlein and Sherry S. Leonard and Edward D. Levin and Ronald J. Lukas and Athina Markou and Michael J. Marks and Sarah E. McCallum and Neeraja Parameswaran and Kenneth A. Perkins and Marina R. Picciotto and Maryka Quik and J. E. Rose and Adrian Rothenfluh and William R. Schafer and Ian P. Stolerman and Rachel F. Tyndale and Jeanne M . Wehner and Jeffrey M. Zirger}, journal={Psychopharmacology}, year={2006}, volume={190}, pages={269-319} }