Evidence map›Paper›PMID 31369741›Full record

ArticleNeuropharmacology2019

Why flavored vape products may be attractive: Green apple tobacco flavor elicits reward-related behavior, upregulates nAChRs on VTA dopamine neurons, and alters midbrain dopamine and GABA neuron function.

Alicia J Avelar, Austin T Akers, Zachary J Baumgard, Skylar Y Cooper, Gabriella P Casinelli, Brandon J Henderson

Open access · hybridAbstract read
In one paragraph

Article in Neuropharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Impact of flavorants on nicotine vapor self-administration in adolescent mice: Cherry on top?The Journal of pharmacology and experimental therapeutics · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024
    Article
  13. Article
  14. Review
  15. Article
  16. Chemical Flavorants in Vaping Products Alter Neurobiology in a Sex-Dependent Manner to Promote Vaping-Related Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  17. Review
  18. Article
  19. Morphine Exposure Reduces Nicotine-Induced Upregulation of Nicotinic Receptors and Decreases Volitional Nicotine Intake in a Mouse Model.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Alicia J AvelarDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Austin T AkersDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Zachary J BaumgardDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Skylar Y CooperDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Gabriella P CasinelliDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Brandon J HendersonDepartment of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA. Electronic address: Hendersonbr@marshall.edu.
Marshall University · US

Funding

Characterization of menthol's effect on nicotine reward and nicotinic receptor neurobiologyR00DA040047 · NIDA · MARSHALL UNIVERSITY · PI HENDERSON, BRANDON JARROD · 2017 to 2019
$650k
alpha4alpha6 nicotinic receptors: biomarkers for nicotine addictionR21DA046335 · NIDA · MARSHALL UNIVERSITY · PI HENDERSON, BRANDON JARROD · 2018 to 2019
$405k
Characterization of menthol's effect on nicotine reinforcement and nicotinic receptor neurobiologyK99DA040047 · NIDA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI HENDERSON, BRANDON JARROD · 2016 to 2016
$151k
NIDA NIH HHS K99 DA040047NIDA NIH HHS R00 DA040047NIDA NIH HHS R21 DA046335
6 · The paper itself

Abstract

While nicotine is the primary addictive component in tobacco products, additional flavors have become a concern with the growing popularity of electronic nicotine delivery systems (ENDS). For this reason, we have begun to investigate popular tobacco and ENDS flavors. Here, we examined farnesol, a chemical flavorant used in green apple and fruit flavors in ENDS e-liquids, for its ability to produce reward-related behavior. Using male and female 3-6 month old C57BL/6 J mice and farnesol doses of 0.1, 1, and 10 mg/kg we identified a sex-dependent effect in a conditioned place preference assay: farnesol-alone produces reward-related behavior in only male mice. Despite this sex-dependent effect, 1.0 mg/kg farnesol enhances locomotor activity in both male and female mice. To understand farnesol's effect on reward-related behavior, we used whole-cell patch-clamp electrophysiology and confocal microscopy to investigate changes in putative dopamine and GABA neurons. For these approaches, we utilized genetically modified mice that contain fluorescent nicotinic acetylcholine receptors (nAChRs). Our electrophysiological assays with male mice revealed that farnesol treatment increases ventral tegmental area (VTA) dopamine neuron firing frequency and this may be due to a decrease in inhibitory tone from GABA neurons. Our microscopy assays revealed that farnesol treatment produces a significant upregulation of α6* nAChRs in male mice but not female mice. This was supported by an observed increase in α6* nAChR function in additional electrophysiology assays. These data provide evidence that popular tobacco flavorants may alter smoking-related behavior and promote the need to examine additional ENDS flavors.

Indexed as

RewardAnimalsBehavior, AnimalConditioning, PsychologicalDopaminergic NeuronsElectronic Nicotine Delivery SystemsFarnesolFemaleFlavoring AgentsGABAergic NeuronsLocomotionMaleMesencephalonMiceMicroscopy, ConfocalNicotineChrna6 protein, mouseFarnesolFlavoring AgentsNicotineNicotinic AgonistsReceptors, NicotinicAddictionConditioned place preferenceDopamine neuronElectrophysiologyFlavorantsGABA neuronMicroscopyNicotinic receptorsTobaccoVaping

Identifiers

PMID31369741
PMCPMC6751572
OpenAlexW2965770623

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.