Nicotine formulations impact reinforcement-related behaviors in a mouse model of vapor self-administration

Abstract

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.

Keywords: Animal models; Nicotine formulations; Reinforcement; Self-administration.

Figure 1.

Daily FR1 and FR3 EVSA nosepokes for male (A) and female (C) mice. Symbol colors indicate e-liquid assignment (green, nicotine + menthol; grey, nicotine-freebase (FB); bronze, nicotine-salt; white, PGVG (vehicle control); and black, inactive nosepokes). Green squares indicate sessions where mice were re-baselined to nicotine + menthol. Mean FR3 EVSA deliveries for male (B) and female (D) mice that were assigned PGVG (vehicle), nicotine- FB, or nicotine-salt. *, p<0.05; **, p<0.01; and ***, p<0.001. All data are Mean ± SEM.

Figure 2.

Plasma cotinine levels of male (A) and female (B) mice that were assigned PGVG, nicotine-FB,or nicotine-salt following a single passive e-Vape® session. Data are mean ± SEM. *, p<0.05; **, p<0.01.