# Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $439,112

## Abstract

E-cigarettes are increasingly used by teenagers, who are particularly vulnerable to the addictive
properties of nicotine. With the exclusion of menthol, the use of flavor additives has been banned from
traditional cigarettes, while e-cigarettes are marketed in over 7,000 different flavors. Many of those
flavors are found in candy and popular soft drinks and, because they are familiar, make e-cigarettes
more appealing to adolescents. We hypothesize that flavorants enhance nicotine reward through
sensory and/or natural reward mechanisms. As a consequence, flavored e-cigarettes may promote
nicotine experimentation, dependence, and eventually, the use of regular cigarettes. Understanding
how flavors influence e-cigarette use is important for the implementation of regulatory rules that can
reduce potential disease and death deriving from the consumption of this increasingly popular tobacco
product.
The goal of this application is to compare the rewarding and reinforcing properties of flavored
vs. non-flavored e-cigarettes in adolescent mice. Our hypothesis is that flavored e-cigarettes are more
rewarding than non-flavored e-cigarettes, and that flavor additives promote and sustain nicotine
seeking in adolescents. The first goal is to determine whether sweet flavorants enhance adolescent
nicotine reward and promote nicotine self-administration. The second goal is to investigate the
possibility that a learned flavor preference, which models exposure to sweetened food and beverages
at a young age, will further enhance flavor-induced nicotine reward and self-administration. Finally, we
will determine whether exposure to flavored e-cigarettes at young age increases the risk of nicotine
abuse in adulthood. These behavioral experiments will be complemented by a series of molecular
investigations. First, we will employ in vivo tetrode recording to measure changes in dopamine neuron
firing during exposure to flavored and non-flavored e-cig nicotine vapor. Second, we will utilize in vivo
voltammetry techniques to quantitatively measure dopamine release in the NAc in response to
inhalation of flavored vs.unflavored e-cigarette vapors. Third, we will utilize state-of-the art approaches
to determine whether e-cigarette nicotine vapor changes the epigenetic landscape of reward-
associated brain areas, and weather fruit flavorants have additive or synergistic effects.

## Key facts

- **NIH application ID:** 10074554
- **Project number:** 5R01DA044205-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mariella De Biasi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $439,112
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074554

## Citation

> US National Institutes of Health, RePORTER application 10074554, Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms (5R01DA044205-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074554. Licensed CC0.

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