Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats

Andrew C. Harris, P. Muelken, Yayi Swain, Mary Palumbo, V. Jain, Maciej L. Goniewicz, I. Stepanov, Mark G. LeSage

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Development of preclinical methodology for evaluating the abuse liability of electronic cigarettes (ECs) in adolescents is urgently needed to inform FDA regulation of these products. We previously reported reduced aversive effects of EC liquids containing nicotine and a range of non-nicotine constituents (e.g., propylene glycol, minor tobacco alkaloids) compared to nicotine alone in adult rats as measured using intracranial self-stimulation. The goal of this study was to compare the aversive effects of nicotine alone and EC aerosol extracts in adolescent rats as measured using conditioned taste aversion (CTA), which can be conducted during the brief adolescent period. Methods and Results: In Experiment 1, nicotine alone (1.0 or 1.5 mg/kg, s.c.) produced significant CTA in adolescent rats in a two-bottle procedure, thereby establishing a model to study the effects of EC extracts. At a nicotine dose of 1.0 mg/kg, CTA to Vuse Menthol EC extract, but not Aroma E-Juice EC extract, was attenuated compared to nicotine alone during repeated two-bottle CTA tests (Experiment 2a). At a nicotine dose of 0.5 mg/kg, CTA to Vuse Menthol EC extract did not differ from nicotine alone during the first two-bottle CTA test but extinguished more rapidly across repeated two-bottle tests (Experiment 2b). Conclusions: Non-nicotine constituents in Vuse Menthol EC extracts attenuated CTA in a two-bottle procedure in adolescents. This model may be useful for anticipating the abuse liability of ECs in adolescents and for modeling FDA-mandated changes in product standards for nicotine or other constituents in ECs.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalDrug and alcohol dependence
Volume203
DOIs
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
Funding for this study was provided by NIH/NIDA grant RO3 DA042009 (Harris, AC, PI), NIDA training grant T32 DA007097 (Swain, Y; Molitor T, PI) and the Hennepin Healthcare Research Institute (formerly Minneapolis Medical Research Foundation) Career Development Award (LeSage, MG, Harris, AC). These funding institutions had no role in the study design, data collection, data analysis, interpretation of the data, manuscript preparation, or decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Food and Drug Administration. The authors thank Danielle Motz, Annika Skansberg, Zach Haave, and Haley Rudnick for their excellent technical assistance in conducting the behavioral experiments. We also thank Drs. Linda von Weymarn and Sharon Murphy for conducting the ?-nicotyrine analysis.

Funding Information:
Funding for this study was provided by NIH/NIDA grant RO3 DA042009 (Harris, AC, PI), NIDA training grant T32 DA007097 (Swain, Y; Molitor T, PI) and the Hennepin Healthcare Research Institute (formerly Minneapolis Medical Research Foundation) Career Development Award (LeSage, MG, Harris, AC). These funding institutions had no role in the study design, data collection, data analysis, interpretation of the data, manuscript preparation, or decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Food and Drug Administration.

Publisher Copyright:
© 2019

Keywords

  • Adolescents
  • Conditioned taste aversion
  • Electronic cigarettes
  • Nicotine
  • Non-nicotine tobacco constituents

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