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Published on: May 30, 2025
Nicotine formulations impact reinforcement-related behaviors in a mouse model of vapor self-administration
Brandon J Henderson1, Skylar Y Cooper1
1Department of Biomedical Sciences, Joan C Edwards School of Medicine at Marshall University, 1700 3(rd) ave, Huntington, WV, 25703, USA.
Background:
Electronic nicotine delivery systems (ENDS) differ from combustible cigarettes given that nicotine-salt or nicotine-freebase may be used depending on the product. We have investigated how nicotine-salt and freebase formulations alter e-Vape® self-administration (EVSA) behavior and plasma cotinine levels in male and female mice.
Methods:
Adult C57/BL6 J mice were used in EVSA and assigned vaping e-liquids (50:50 PGVG, 6 mg/mL nicotine-freebase, or 6 mg/mL nicotine-salt). Mice were escalated on a fixed ratio 1 (FR1) schedule in daily 2 h sessions and then transitioned to a FR3 to examine reinforcement-related behaviors.
Results:
Here we observed that mice assigned nicotine-salt exhibited increased EVSA on a FR3 schedule compared to nicotine-freebase. Additionally, mice assigned nicotine-salt exhibited higher plasma cotinine concentrations following delivery-controlled passive-inhalation sessions.
Conclusions:
These data provide evidence nicotine-salt formulations may contribute to greater reinforcement-related behavior and highlight the need for further investigations regarding nicotine formulation in ENDS.
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