DOI
https://doi.org/10.25772/N6MP-ZG40
Defense Date
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmacology & Toxicology
First Advisor
Keith Shelton
Second Advisor
Joseph Porter
Third Advisor
Matthew Halquist
Fourth Advisor
Jennifer Wolstenholme
Fifth Advisor
Matthew Walentiny
Abstract
Tobacco cigarette smoking has been decreasing in the US and is being replaced by electronic cigarettes (e-cig) also referred to as electronic nicotine delivery systems (ENDS). ENDS are battery-powered devices that heat and aerosolize a liquid mixture constituting of a vehicle, drug, and flavorings. ENDS are often promoted as a smoking cessation aid. Unfortunately, e-cigarettes have become very popular among youth including many who have never used combustible cigarettes. Only a small percentage of teens used e- cigarettes in 2011 but by 2019 use peaked with 28% of high school students and 11% of middle school students reporting e-cigarette use decreased somewhat in 2020 but remains a health issue affecting children, and youth. The rapid increase and high prevalence of e-cigarettes use highlights the importance of developing a scientific, data-driven approach to understanding their potential health implications. Animal models of e-cigarette exposure with pharmacokinetics and vaping parameters resembling human e-cigarette users will be important to scientists, clinicians, and regulators, have not to be adequately developed. The overarching goal of the project was to explore the abuse-related subjective stimulus effects of nicotine aerosol using the drug discrimination procedure in rodents. First, the nature of inhaled nicotine was compared to injected nicotine and the impact of puffing parameters and device power on the DS of inhaled nicotine was assessed. Second, the pharmacological basis underlying nicotine aerosol’s discriminative stimulus was examined. Third, exteroceptive and interoceptive components of the discriminative stimulus of inhaled nicotine was explored. Lastly, the impact of menthol on the discriminative stimulus effect of nicotine aerosol was measured. Inhaled nicotine aerosol produced CNS-mediated discriminative stimulus effects equivalent to those of injected nicotine. Number of puffs and wattage played a role in the stimulus effects of inhaled nicotine, but other variables such as vehicle composition, nicotine forms were not involved. The discriminative stimulus effects of inhaled nicotine were mediated by nicotinic acetylcholine receptors similar to the stimulus of injected nicotine. Menthol enhanced the abuse-related effects of nicotine aerosol, which could provide support for the hypothesis that eliminating menthol from both e-liquids and combustible cigarettes may reduce their abuse liability. Addition of tobacco flavors appeared to have little impact in maintaining nor attenuating the stimulus effects of nicotine aerosol.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2023