Menthol enhances the strength and duration of nicotine's effects in rats
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Menthol, a common flavoring for traditional cigarettes and e-cigarettes, may do more than change how nicotine tastes or feels. New research published in ACS Chemical Neuroscience reports that male rats exposed to menthol-containing e-cigarette aerosols experienced nicotine's effects more strongly and for longer than rats exposed to nicotine alone. The findings provide insight into how menthol can modify the effects of inhaled nicotine.
Evidence suggests that, in addition to providing a cooling flavor, menthol can influence nicotine-related responses in the body and in behavior. However, less is known about how menthol modifies nicotine's effects when the two are delivered together in an e-cigarette aerosol. To address this, Seong Shoon Yoon, Sooyeun Lee and colleagues explored the interactions in rats.
Testing combined aerosol exposure
The researchers made their own e-cigarette liquids containing nicotine and menthol as the only flavoring. They used 81 male rats to examine the effects of nicotine and menthol aerosols. During exposure, the rats were placed in a clear chamber, and aerosols containing nicotine, menthol or both were delivered at five-minute intervals using a commercial e-cigarette device. The number of puffs varied by experiment.
After inhalation, the researchers measured nicotine and byproducts of nicotine metabolism in the rats' blood and tracked changes in body temperature, a well-established nicotine response in rodents. Compared with nicotine alone, menthol and nicotine together:
- Prolonged the nicotine-induced drop in body temperature, with the groups still differing significantly 120 minutes after exposure.
- Made nicotine's effects more noticeable to the rats.
- Produced higher levels of some nicotine byproducts in the rats' blood than nicotine-only aerosols did.
Menthol's role beyond flavor
"The most important takeaway is that menthol should not be viewed merely as a passive flavor additive," Yoon said. "Our findings in male rats show that it changes both the intensity and the duration of nicotine's physiological and internal drug-cue effects."
Next, the researchers plan to investigate exactly how menthol changes nicotine-related signaling in the brain and whether the effects differ between male and female rats.
Publication details
Tae In Eom et al, Body Temperature and Discriminative Stimulus Effects of Nicotine and Menthol Aerosols in Male Rats: Role of α4β2 Nicotinic Acetylcholine Receptors, ACS Chemical Neuroscience (2026). DOI: 10.1021/acschemneuro.6c00295
Journal information: ACS Chemical Neuroscience
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