Flavorants enhance nicotine vapor self-administration in diet-induced obese female mice

Nicotine dependence and obesity are global health issues. Emerging studies suggest that obese individuals are more likely to develop nicotine dependence. Despite this knowledge, there have been few investigations into whether nicotine dose and/or chemical flavorants commonly found in nicotine-containing products modulate nicotine dependence in obese models. Therefore, our objective was to examine whether low (6 mg/mL) or high (60 mg/mL) dose nicotine, with or without flavor impact vaping-related behaviors in a diet-induced obesity (DIO) mouse model. Briefly, adult male and female DIO mice were trained to self-administer 6 or 60 mg/mL nicotine, with or without menthol and green apple (GA) flavors using an e-Vape self-administration assay. Overall, DIO female mice assigned to flavored e-liquids self-administered more nicotine than their male counterparts. Additionally, DIO female mice assigned to 6 mg/mL nicotine + menthol exhibited higher nicotine reinforcement-related behavior than female mice assigned 6 mg/mL nicotine (unflavored). Reinforcement-related behavior was not changed in DIO male mice assigned to e-liquids containing 60 mg/mL nicotine. However, DIO female mice exhibited menthol- and GA-induced enhancements in reinforcement-related behavior with 60 mg/mL nicotine. By combining a noncontingent vapor exposure assay with fast-scan cyclic voltammetry, we observed that menthol and GA flavorants, when combined with 6 or 60 mg/mL nicotine, increased tonic- and phasic-stimulated dopamine signaling in the nucleus accumbens core. Together, these preclinical findings provide additional evidence that nicotine plus popular chemical flavorants such as menthol and GA could alter dopamine signaling in the reward pathway and promote vaping-related behaviors in a DIO mouse model. SIGNIFICANCE STATEMENT: This study highlights the effects of flavorants on vaping-related behaviors in a diet-induced obese mouse model. Collectively, this study revealed that flavorants commonly found in vaping products alter dopamine release in the nucleus accumbens core-a phenomenon linked with nicotine addiction.