Menthol prolongs nicotine effects in rats exposed to e-cigarettes

Menthol, a common flavoring for both traditional cigarettes and e-cigarettes, may do more than simply 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, comparatively 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. 

The researchers made their own e-cigarette liquids containing nicotine and menthol as the only flavoring. For the study, they used 81 male rats to examine the effects of nicotine and menthol aerosols. During aerosol exposure, rats were placed in a clear chamber, and nicotine and/or menthol aerosols were delivered at five-minute intervals using a commercial e-cigarette device, with the number of puffs varying by experiment. 

After inhalation, the researchers measured nicotine and nicotine metabolism by-products 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 at 120 minutes after exposure. 

• Made nicotine's effects more noticeable to the rats 

• Higher levels of some nicotine by-products in their blood than rats exposed to the nicotine-only aerosols. 

"The most important takeaway is that menthol should not be viewed merely as a passive flavor additive," says Yoon. "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.