Flavor compounds found in electronic cigarette liquids differentially enhance voluntary nicotine consumption and preference in mice.

Introduction: Beta-damascone is a flavor compound found only in tobacco-flavored e-cigarette products, trans-2-hexenal is found only in fruit-flavored products, and isoamyl acetate is found in multiple flavor categories such as fruit, candy and dessert. We investigated the effect of these compounds on nicotine consumption and preference in mice to determine how these compounds modulate nicotine intake.

Methods: Adult, male C57BL/6J mice underwent a voluntary, 24 hour two-bottle choice test where they were presented with 75 μg/mL nicotine, the flavor compounds only (0.1-100 μg/mL), or the flavor compounds plus nicotine over a 5-week period.

Results: Beta-damascone resulted in increased nicotine consumption (mg/kg) and % preference when added to nicotine at 1 μg/mL, whereas trans-2-hexenal had no enhancing effect on nicotine consumption and preference compared with mice that were given nicotine alone. Isoamyl acetate resulted in increased consumption but not preference when added to nicotine at 1 μg/mL. The preference for the three flavor compounds alone was similar and did not differ from water between 0.1 - 50 μg/mL. At 100 μg/mL, the preference for the flavor compounds was significantly less compared with water.

Conclusion: We find that flavor compounds have distinct modulatory effects on nicotine consumption and preference that are not due to increased preference for the flavor itself. Moreover, flavor compounds in the same flavor category (e.g. trans-2-hexenal and isoamyl acetate) do not have the same effects, indicating that the modulatory effect of flavor compounds cannot be generalized based on their category.

Implications: This study examines the effect of individual flavor compounds on nicotine consumption and preference in a preclinical mouse model. We find that flavor compounds have distinct effects in modulating nicotine consumption and preference in mice, with flavor compounds of the same flavor category having differential modulatory effects. These data suggest that the effect of flavor compound cannot be generalized to the flavor category.