Abuse liability assessment of an e-cigarette refill liquid using intracranial self-stimulation and self-administration models in rats

M. G. LeSage, M. Staley, P. Muelken, J. R. Smethells, I. Stepanov, R. I. Vogel, P. R. Pentel, A. C. Harris

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background The popularity of electronic cigarettes (ECs) has increased dramatically despite their unknown health consequences. Because the abuse liability of ECs is one of the leading concerns of the Food and Drug Administration (FDA), models to assess it are urgently needed to inform FDA regulatory decisions regarding these products. The purpose of this study was to assess the relative abuse liability of an EC liquid compared to nicotine alone in rats. Because this EC liquid contains non-nicotine constituents that may enhance its abuse liability, we hypothesized that it would have greater abuse liability than nicotine alone. Methods Nicotine alone and nicotine dose-equivalent concentrations of EC liquid were compared in terms of their acute effects on intracranial self-stimulation (ICSS) thresholds, acquisition of self-administration, reinforcing efficacy (i.e., elasticity of demand), blockade of these behavioral effects by mecamylamine, nicotine pharmacokinetics and nicotinic acetylcholine receptor binding and activation. Results There were no significant differences between formulations on any measure, except that EC liquid produced less of an elevation in ICSS thresholds at high nicotine doses. Conclusions Collectively, these findings suggest that the relative abuse liability of this EC liquid is similar to that of nicotine alone in terms of its reinforcing and reinforcement-enhancing effects, but that it may have less aversive/anhedonic effects at high doses. The present methods may be useful for assessing the abuse liability of other ECs to inform potential FDA regulation of those products.

Original languageEnglish (US)
Pages (from-to)76-88
Number of pages13
JournalDrug and alcohol dependence
StatePublished - Nov 1 2016

Bibliographical note

Funding Information:
Funding for this study was provided by NIH/NCI grant U19-CA157345 (Hatsukami DH and Shields P, MPI; LeSage MG, PL), NIDA training grant T32 DA007097 (Smethells, JR; Molitor T, PI), and a Career Development Award (MGL) and Translational Research Program (ACH) from the Minneapolis Medical Research Foundation . These funding institutions had no role in the study design, data collection, data analysis, interpretation of the data, manuscript preparation, or decisions to submit the manuscript for publication.

Funding Information:
The authors thank Danielle Burroughs, Laura Tally, Theresa Harmon, Clare Schmidt, Christine Egan, and Andrew Banal for their excellent technical assistance in conducting the experiment. The authors also thank Drs. Steven Hursh and Pete Roma from the Institutes for Behavior Resources (Baltimore, MD) and Johns Hopkins University School of Medicine for providing the software for demand curve analysis and their assistance with conducting the analysis. Ki determinations and agonist/antagonist functional data were generously provided by the National Institute of Mental Health's Psychoactive Drug Screening Program, Contract # HHSN-271-2008-00025-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscol at NIMH, Bethesda MD, USA. Preliminary data from this study were presented at the 22nd Annual Meeting of the Society for Research on Nicotine and Tobacco, Chicago, IL; March 2016.


  • Behavioral economics
  • E-cigarettes
  • Intracranial self-stimulation
  • Nicotine
  • Rat
  • Self-administration
  • Tobacco control policy


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