Guidelines on nicotine dose selection for in vivo research

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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 comprising species-specific in vivo responses to acute or chronic nicotine exposure. The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose–response relationships. The review addresses seven species: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish, focusing on issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses. The review provides a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models.