Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters

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Abstract

Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.

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Large-scale functional or structural brain connectivity can be modeled as a network, or graph. This paper presents a statistical approach to identify connections in such a graph that may be associated with a diagnostic status in case-control studies, changing psychological contexts in task-based studies, or correlations with various cognitive and behavioral measures. The new approach, called the network-based statistic (NBS), is a method to control the family-wise error rate (in the weak sense) when mass-univariate testing is performed at every connection comprising the graph. To potentially offer a substantial gain in power, the NBS exploits the extent to which the connections comprising the contrast or effect of interest are interconnected. The NBS is based on the principles underpinning traditional cluster-based thresholding of statistical parametric maps. The purpose of this paper is to: (i) introduce the NBS for the first time; (ii) evaluate its power with the use of receiver operating characteristic (ROC) curves; and, (iii) demonstrate its utility with application to a real case-control study involving a group of people with schizophrenia for which resting-state functional MRI data were acquired. The NBS identified a expansive dysconnected subnetwork in the group with schizophrenia, primarily comprising fronto-temporal and occipito-temporal dysconnections, whereas a mass-univariate analysis controlled with the false discovery rate failed to identify a subnetwork. Copyright © 2010 Elsevier Inc. All rights reserved.

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Vaping versus JUULing: how the extraordinary growth and marketing of JUUL transformed the US retail e-cigarette market

Jidong Huang, Zongshuan Duan, Julian Kwok … (2018)

Background While national surveys showed declines in e-cigarette use in the USA between 2015 and 2016, recent reports indicate that JUUL, a sleekly designed e-cigarette that looks like a USB drive, is increasingly being used by youth and young adults. However, the extent of JUUL’s growth and its marketing strategy have not been systematically examined. Methods A variety of data sources were used to examine JUUL retail sales in the USA and its marketing and promotion. Retail store scanner data were used to capture the retail sales of JUUL and other major e-cigarette brands for the period 2011–2017. A list of JUUL-related keywords was used to identify JUUL-related tweets on Twitter; to identify JUUL-related posts, hashtags and accounts on Instagram and to identify JUUL-related videos on YouTube. Results In the short 3-year period 2015–2017, JUUL has transformed from a little-known brand with minimum sales into the largest retail e-cigarette brand in the USA, lifting sales of the entire e-cigarette category. Its US$150 million retail sales in the last quarter of 2017 accounted for about 40% of e-cigarette retail market share. While marketing expenditures for JUUL were moderate, the sales growth of JUUL was accompanied by a variety of innovative, engaging and wide-reaching campaigns on Twitter, Instagram and YouTube, conducted by JUUL and its affiliated marketers. Conclusions The discrepancies between e-cigarette sales data and the prevalence of e-cigarette use from surveys highlight the challenges in tracking and understanding the use of new and emerging tobacco products. In a rapidly changing media environment, where successful and influential marketing campaigns can be conducted on social media at little cost, marketing expenditures alone may not fully capture the influence, reach and engagement of tobacco marketing.

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Author and article information

Contributors

Jibran Y. Khokhar:

ORCID: http://orcid.org/0000-0002-2169-2275

jkhokha@uwo.ca

Journal

Journal ID (nlm-ta): Neuropsychopharmacology

Journal ID (iso-abbrev): Neuropsychopharmacology

Title: Neuropsychopharmacology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0893-133X

ISSN (Electronic): 1740-634X

Publication date (Electronic): 7 December 2023

Publication date PMC-release: 7 December 2023

Publication date (Print): April 2024

Volume: 49

Issue: 5

Pages: 782-795

Affiliations

[1 ]GRID grid.34429.38, ISNI 0000 0004 1936 8198, Department of Biomedical Sciences, Ontario Veterinary College, , University of Guelph, ; Guelph, ON Canada

[2 ]Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, ( https://ror.org/02grkyz14) London, ON Canada

[3 ]Department of Medical Biophysics and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, ( https://ror.org/02grkyz14) London, ON Canada

[4 ]Department of Psychiatry, Faculty of Medicine, University of British Columbia, ( https://ror.org/03rmrcq20) Vancouver, BC Canada

[5 ]GRID grid.155956.b, ISNI 0000 0000 8793 5925, Departments of Psychiatry, and Pharmacology & Toxicology, , University of Toronto, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, ; Toronto, ON Canada

Author information

Rachel F. Tyndale http://orcid.org/0000-0003-1297-2053

Jibran Y. Khokhar http://orcid.org/0000-0002-2169-2275

Article

Publisher ID: 1773

DOI: 10.1038/s41386-023-01773-3

PMC ID: 10948865

PubMed ID: 38057369

SO-VID: b7ba38b2-0e47-4086-be6c-8117d541024d

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 21 May 2023

Date revision received : 5 November 2023

Date accepted : 14 November 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100000024, Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada);

Award ID: Vanier

Award ID: 442011

Award Recipient : Jude A. Frie Jibran Y. Khokhar

Funded by: FundRef https://doi.org/10.13039/501100001804, Canada Research Chairs (Chaires de recherche du Canada);