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Drug Alcohol Depend. 2018 Apr 1;185:1-9. doi: 10.1016/j.drugalcdep.2017.11.032. Epub 2018 Feb 1.

Effects of nicotine-containing and "nicotine-free" e-cigarette refill liquids on intracranial self-stimulation in rats.

Author information

1
Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA. Electronic address: harr0547@umn.edu.
2
Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, USA.
3
Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, USA; Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
4
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
5
Department of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, USA.
6
Department of Medicine, Minneapolis Medical Research Foundation, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.

Abstract

BACKGROUND:

Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs).

METHODS AND RESULTS:

Nicotine alone and nicotine dose-equivalent concentrations of both nicotine-containing EC liquids produced similar lowering of ICSS thresholds at low to moderate nicotine doses, indicating similar reinforcement-enhancing effects. At high nicotine doses, nicotine alone elevated ICSS thresholds (a measure of anhedonia-like behavior) while the EC liquids did not. Nicotine-containing EC liquids did not differ from nicotine alone in terms of binding affinity or functional activity at nAChRs. "Nicotine-free" EC liquids did not affect ICSS, but bound with low affinity at some (e.g., α4ß2) nAChRs.

CONCLUSIONS:

These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs.

KEYWORDS:

Electronic cigarettes; Intracranial self-stimulation; Nicotine; Non-nicotine tobacco constituents; Tobacco control policy

PMID:
29413432
PMCID:
PMC5889751
[Available on 2019-04-01]
DOI:
10.1016/j.drugalcdep.2017.11.032
[Indexed for MEDLINE]

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