ArticleeNeuro
Green Apple e-Cigarette Flavorant Farnesene Triggers Reward-Related Behavior by Promoting High-Sensitivity nAChRs in the Ventral Tegmental Area.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Synthetic cooling agents enhance nicotine reinforcement and mesolimbic dopamine signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Impact of flavorants on nicotine vapor self-administration in adolescent mice: Cherry on top?The Journal of pharmacology and experimental therapeutics · 2025Article
- Impact of chemical flavorants on reinforcement-related behavior in an adolescent mouse model of vaping self-administration.The Journal of pharmacology and experimental therapeutics · 2025Article
- Longitudinal Associations between Adolescent Electronic Cigarette Use and Eating Behaviors.Substance use & misuse · 2025Article
- Age-dependent effects of vaping on the prefrontal cortex, ventral tegmental area, and nucleus accumbens.Communications biology · 2024Article
- 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 · 2024Article
- Flavoring Agents in E-cigarette Liquids: A Comprehensive Analysis of Multiple Health Risks.Cureus · 2023Review
- 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 · 2023Article
- Beyond the label: current evidence and future directions for the interrelationship between electronic cigarettes and mental health.Frontiers in psychiatry · 2023Review
- 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 · 2022Article
- Genotypic Differences in the Effects of Menthol on Nicotine Intake and Preference in Mice.Frontiers in neuroscience · 2022Article
- Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and Dependence.Current neuropharmacology · 2022Review
- Chemosensory Contributions of E-Cigarette Additives on Nicotine Use.Frontiers in neuroscience · 2022Review
- The Impact of Electronic Nicotine Delivery System (ENDS) Flavors on Nicotinic Acetylcholine Receptors and Nicotine Addiction-Related Behaviors.Molecules (Basel, Switzerland) · 2020Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
While combustible cigarette smoking has declined, the use of electronic nicotine delivery systems (ENDS) has increased. ENDS are popular among adolescents, and chemical flavorants are an increasing concern because of the growing use of zero-nicotine flavored e-liquids. Despite this, little is known regarding the effects of ENDS flavorants on vaping-related behavior. Following previous studies demonstrating the green apple flavorant, farnesol, enhances nicotine reward and exhibits rewarding properties without nicotine, this work focuses on the green apple flavorant, farnesene, for its impact on vaping-related behaviors. Using adult C57BL/6J mice, genetically modified to contain fluorescent nicotinic acetylcholine receptors (nAChRs), and farnesene doses of 0.1, 1.0, and 10 mg/kg, we observed farnesene-alone produces reward-related behavior in both male and female mice. We then performed whole-cell patch-clamp electrophysiology and observed farnesene-induced inward currents in ventral tegmental area (VTA) putative dopamine (pDA) neurons that were blocked by the nAChR antagonist, DhβE. While the amplitudes of farnesene-induced currents are ∼30% of nicotine's efficacy, this indicates the potential for some ENDS flavorants to stimulate nAChR function. Additionally, farnesene enhances nicotine's potency for activating nAChRs on VTA dopamine neurons. This may be because of changes in nAChR stoichiometry as our data suggest a shift toward high-sensitivity α4β2 nAChRs. Consequently, these data show that the green apple flavorant, farnesene, causes reward-related behavior without nicotine through changes in nAChR stoichiometry that results in an enhanced effect of nicotine on VTA dopamine neurons. These results demonstrate the importance of future investigations into ENDS flavorants and their effects on vaping-related behaviors.
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Registered trials
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.