Behavioral and pharmacokinetic assessment of nicotine e-cigarette inhalation in female rats

Nicole M Roeder; Abrianna Mihalkovic; Brittany J Richardson; Samantha L Penman; Maria Novalen; Nikki Hammond; Rina Eiden; Jibran Y Khokhar; Rachel F Tyndale; Panayotis K Thanos

doi:10.1093/ntr/ntad240

Behavioral and pharmacokinetic assessment of nicotine e-cigarette inhalation in female rats

Nicotine Tob Res. 2023 Dec 13:ntad240. doi: 10.1093/ntr/ntad240. Online ahead of print.

Authors

Nicole M Roeder^{1

2}, Abrianna Mihalkovic^{1

2}, Brittany J Richardson^{1

2}, Samantha L Penman¹, Maria Novalen³, Nikki Hammond¹, Rina Eiden⁴, Jibran Y Khokhar⁵, Rachel F Tyndale³, Panayotis K Thanos^{1

2}

Affiliations

¹ Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY USA.
² Department of Psychology, University at Buffalo, Buffalo, NY USA.
³ Center for Addiction and Mental Health and Department of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, ON, Canada.
⁴ Department of Psychology, Social Science Research Institute, The Pennsylvania State University, University Park, PA 16801, USA.
⁵ Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, ON, Canada.

PMID: 38092656
DOI: 10.1093/ntr/ntad240

Abstract

Introduction: Nicotine and tobacco use remain high both globally and in the USA, contributing to large healthcare expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure. This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics.

Methods: We tested two inhalation doses of nicotine (24 mg/ml and 59 mg/ml) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC-MS/MS.

Results: showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend.

Conclusions: Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure.

Implications: This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.

Keywords: e-cigarette; liquid chromatography-mass spectrometry; nicotine; subcutaneous injection; vapor inhalation.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.