Green Apple Flavor in Vapes Enhances Nicotine Reward

This is a diagram from the study
The green apple vape flavorant, farnesene, is rewarding in mice as demonstrated through a three-chamber Pavlovian choice behavioral task. Green apple promotes the inclusion of high-sensitivity nicotinic receptors to a greater extent than low-sensitivity receptors. This enhances nicotine's impact in brain regions that are critical in nicotine addiction. Image is credited to Cooper et al., eNeuro 2020.

Summary: Common green apple flavorant farnesene enhances nicotine reward in mouse models. The flavorant is also rewarding on its own. Researchers say with or without nicotine, flavored vapes, especially those containing farnesene, pose potential neurological risks, including addiction.

Source: SfN

A common green apple vape flavor enhances nicotine reward and is also rewarding itself, according to research in mice recently published in eNeuro.

Vaping entices adolescents into nicotine use with fun flavors like green apple and cotton candy. Nicotine-free flavored vapes have also gained popularity. But of the over 7000 available flavor chemicals, only a handful have been studied. With or without nicotine, flavored vapes pose potential risks for the brain, including addiction.

To continue unravelling these risks, Cooper et al. gave mice either nicotine, the green apple flavorant farnesene, or both in one chamber and a saline solution in another. Farnesene was rewarding by itself, as mice chose the farnesene chamber over the saline chamber. But farnesene also enhanced reward when combined with nicotine.

The research team next measured how farnesene changed nicotine receptor expression and neuron activation. Alone, farnesene partially activated nicotinic receptors, meaning it may increase nicotine’s receptor activation when both substances are present. Farnesene also increased the proportion of high- to low-sensitivity receptors. A greater proportion of high-sensitivity receptors increases the effects of a standard nicotine dose, which could heighten reward and drug-seeking behavior. Despite their marketing, vape flavors are not risk-free and may exacerbate the effects of nicotine.

About this neuroscience research article

Media Contacts:
Calli McMurray – SfN
Image Source:
The image is credited to Cooper et al., eNeuro 2020.

Original Research: Open access
“Green Apple E-Cigarette Flavorant Farnesene Triggers Reward-Related Behavior by Promoting High-Sensitivity nAChRs in the Ventral Tegmental Area” by Skylar Y. Cooper, Austin T. Akers and Brandon J. Henderson. eNeuro.


Green Apple E-Cigarette Flavorant Farnesene Triggers Reward-Related Behavior by Promoting High-Sensitivity nAChRs in the Ventral Tegmental Area

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 due to 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 nicotine 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 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 due to changes in nAChR stoichiometry as our data suggests 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.


Although combustible cigarette use has decreased by ∼11% in America over the past two decades, the use of electronic nicotine delivery systems (ENDS) has increased by 135% and 218% among high school and middle school students, respectively, in the last two years alone (Cullen et al., 2018; 2019). Due to the fact that most ENDS users vape flavored nicotine products and the growing use of zero-nicotine flavored e-liquids, it raises the questions of how chemical flavorants alter nicotine addiction and if they increase abuse liability themselves. We show that one chemical flavorant and odorant of green apple, farnesene, causes reward-related behavior on its own. These results increase our understanding on how flavorants promote neurological changes and affect nicotine addiction.

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