Flavored Vapes Trigger Reward Centers Even Without Nicotine

Summary: A new study shows that some e-cigarette flavorings, like vanilla and cherry, can trigger reward-seeking behaviors in adolescent mice even without nicotine. Researchers found that these flavors alone could activate the brain’s dopamine system, raising concerns about their potential for fostering addiction-like behavior.

Vanilla-flavored vapor, in particular, significantly reinforced such behaviors independent of nicotine. These findings highlight how flavored vaping products, even marketed as nicotine-free, may still pose risks for teens.

Key Facts:

  • Flavor Effects Alone: Vanilla and cherry flavors increased reward behaviors even without nicotine.
  • Brain Impact: Flavors influenced the dopamine system and nicotinic receptors tied to addiction.
  • Youth Risk: Flavored nicotine-free vapes may still encourage addiction-like patterns in teens.

Source: Marshall University

A new study led by researchers at the Marshall University Joan C. Edwards School of Medicine reveals that flavor additives commonly used in e-cigarettes may increase the likelihood of vaping behavior in adolescents—even in the absence of nicotine. 

Published earlier this month in the Journal of Pharmacology and Experimental Therapeutics, the preclinical study found that certain popular flavorings, including vanilla and cherry, can drive reinforcement-related behaviors similar to those associated with nicotine exposure, particularly in adolescents. 

The research further explored how these flavor chemicals interact at the molecular level, showing that green apple and vanilla compounds can affect nicotinic acetylcholine receptor (nAChR) function—proteins known to play a central role in nicotine addiction. Credit: Neuroscience News

Researchers tested the effects of flavored vapor—including combinations with and without nicotine—on male and female adolescent mice. The study employed the e-Vape® self-administration (EVSA) assay, a novel behavioral model that allows mice to voluntarily inhale flavored aerosols.

Mice exposed to vanillin or benzaldehyde demonstrated significantly more active responses compared to controls, despite the absence of nicotine. 

Four flavor-nicotine combinations showed increased reinforcement-related behaviors: nicotine with menthol, cherry or vanilla, as well as vanilla flavor alone. Even in the absence of nicotine, vanilla-flavored vapor alone was sufficient to trigger behavior indicative of reward-seeking, while cherry flavor alone was not. 

“These findings are significant because they demonstrate that some electronic nicotine delivery systems (ENDS) flavors can modulate the brain’s dopamine system—specifically in the nucleus accumbens, a key reward center—even without nicotine present,” said lead investigator Brandon J. Henderson, Ph.D., associate professor of biomedical sciences at the Joan C. Edwards School of Medicine.

“This raises important questions about the potential for addiction-like behaviors in adolescents who use flavored vape products marketed as nicotine-free.” 

The research further explored how these flavor chemicals interact at the molecular level, showing that green apple and vanilla compounds can affect nicotinic acetylcholine receptor (nAChR) function—proteins known to play a central role in nicotine addiction. 

These findings add to a growing body of research showing that flavorings appear to actively alter the brain’s response to nicotine in ways that could increase dependence—especially among youth, Henderson said.

In addition to Henderson, co-authors on the study include Marshall University medical students Dami Adeshina, Gabrielle Hammers, Sean Hill, Sydney McSweeney, Sabrina Swenson, and Sarah Maddox.

The co-authors also include Marshall University Ph.D. students Nathan Olszewski and Samuel Tetteh-Quarshie.

Funding: The study was made possible with funding support from the National Institute on Drug Abuse (DA050717).

About this neuroscience research news

Author: Sheanna Spence
Source: Marshall University
Contact: Sheanna Spence – Marshall University
Image: The image is credited to Neuroscience News

Original Research: Open access.
Impact of chemical flavorants on reinforcement-related behavior in an adolescent mouse model of vaping self-administration” by Brandon J. Henderson et al. Journal of Pharmacology and Experimental Therapeutics


Abstract

Impact of chemical flavorants on reinforcement-related behavior in an adolescent mouse model of vaping self-administration

Electronic nicotine delivery systems (ENDS) are a unique from combustible cigarettes due to the availability of flavor options which make these devices more attractive.

Prior preclinical investigations have determined that menthol and green apple flavorants can enhance nicotine reward and reinforcement by altering dopamine (DA) transmission via nicotinic receptor (nAChR) modulation in reward-mediating brain areas.

In this study, we investigated the impact of vanilla (vanillin and ethyl vanillin) and cherry (ethyl vanillin, vanillin, ethyl acetate, ethyl maltol, and maltol) flavors on reinforcement-related behavior with and without nicotine.

Male and female adolescent C57BL/6J mice were used in an e-Vape® self-administration (EVSA) assay. Four combinations were shown to increase reinforcement-related behavior: nicotine plus menthol, nicotine plus cherry, nicotine plus vanilla, and vanilla alone.

We observed that zero-nicotine cherry-flavored ENDS did not produce robust reinforcement-related behavior when compared to control vapor.

We observed that zero-nicotine vanilla-flavored ENDS did produce reinforcement-related behavior in adolescent male and female mice; the addition of nicotine did not produce a significant difference in active nose pokes or deliveries but did have increased active to inactive ratio.

Additionally, we found that vanilla alone was able to modulate tonic and phasic release of dopamine in the nucleus accumbens (NAc) core.

We also looked at the physical interactions of green apple and vanilla flavors on nicotinic subunits.

These data provide additional evidence that some chemical flavors promote vaping-related behaviors without the inclusion of nicotine.