Flavors Enhance Nicotine Vapor Self-administration in Male Mice

Nicotine Tob Res. 2021 Feb 16;23(3):566-572. doi: 10.1093/ntr/ntaa165.


Introduction: Although the use of combustible cigarettes has decreased in many urban regions of America, the use of electronic nicotine delivery systems (ENDS) has dramatically increased. ENDS, or electronic cigarettes (e-cigarettes), differ from combustible cigarettes given that there are no restrictions on flavorant additives in e-liquids. With 95% of ENDS users vaping flavored e-liquids, it is critical to understand how flavors alter vaping-related behaviors. We have previously shown that menthol and green apple flavors enhance nicotine reward-related behavior in a mouse model and in the present study have investigated how menthol and green apple flavors alter e-Vape self-administration behavior in male mice.

Methods: Adult C57/BL6J male mice were used in vapor-inhalation self-administration assays. Mice were assigned vaping e-liquids (6 mg/mL nicotine with or without menthol or green apple flavor) to escalate on a fixed-ratio 1 (FR1) schedule in daily 3-hour sessions to examine initiation-related behaviors. Following escalation, mice were transitioned to a FR3 and progressive ratio schedules in 3-hour sessions to examine reinforcement-related behaviors.

Results: Here we observed that male mice exhibited increased rates of self-administration escalation on a FR1 schedule when assigned to flavored e-liquids. Upon transition to FR3, mice continued to exhibit enhanced levels of reinforcement with flavored e-liquids. We also observed that mice self-administer zero-nicotine green apple flavored e-liquids.

Conclusions: These data provide additional evidence that ENDS flavors enhance vaping-related initiation and reinforcement-related behavior and promote the need to continue investigating the role ENDS flavors play in vaping-related behaviors.

Implications: There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our study here shows that flavors significantly enhance the acquisition and reinforcement of vaping-related behavior. This suggests that flavors in electronic nicotine delivery systems significantly increase the risk of addiction-related behaviors among users of vaping products.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation*
  • Animals
  • Flavoring Agents / administration & dosage*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / administration & dosage*
  • Reinforcement, Psychology*
  • Reward*
  • Self Administration*


  • Flavoring Agents
  • Nicotine