Green apple e-cigarette flavorant triggers reward-related behavior in the brain

HUNTINGTON, W.Va. - A common green apple vape flavor enhances nicotine reward, which could heighten reward and drug-seeking behavior, according to researchers at Marshall University.

Of the more than 7,000 available flavored vape chemicals, only a handful have been studied. In a new study recently published in eNeuro, an open access journal for the Society of Neuroscience, the team of Marshall University researchers, including Ph.D. candidate Skylar Cooper, research technician Austin Akers and Assistant Professor Brandon Henderson, Ph.D., identified that the flavorant farnesene in green apple e-cigarettes triggers reward-related behavior by promoting high-sensitivity nAChRs in the ventral tegmental area.

“With or without nicotine, flavored vapes pose potential risks for the brain and addiction,” Cooper said.

Cooper et al. gave mice either nicotine, the green apple flavorant farnesene or both in one room and a saline solution in another. Farnesene was rewarding by itself, as mice chose the farnesene chamber over the saline chamber. However, 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.

“Given a consistent rise in adolescent use of these products and the addiction crisis we are facing throughout this country, it is vital to identify a role that these flavors have in nicotine addiction and how this may impact the developing brain,” Cooper said.

Cooper plans to further her research on the impact flavorants have on nicotine addiction, focusing on age-dependent experiments to determine the impacts these flavors have on the adolescent brain.


This work was supported by the National Institutes on Drug Abuse at the National Institutes of Health (DA040047), FDA Center for Tobacco Products (CTP)(DA046335), startup funds by the Marshall University Research Corporation and the PhRMA Foundation (Predoctoral Fellowship).

Date Posted: Monday, August 17, 2020