Why flavored vape products may be attractive: Green apple tobacco flavor elicits reward-related behavior, upregulates nAChRs on VTA dopamine neurons, and alters midbrain dopamine and GABA neuron function.

Introduction:
This text discusses a study examining the effects of farnesol, a chemical flavorant used in green apple and fruit flavors in electronic nicotine delivery systems (ENDS) e-liquids, on reward-related behavior. The study found that farnesol-alone produces reward-related behavior in male mice, and when combined with nicotine, it enhances nicotine reward-related behavior in both male and female mice. The study also found that farnesol increases ventral tegmental area (VTA) dopamine neuron firing frequency and upregulates α6* nAChRs in male mice.

Key Points:

* The study used male and female 3 – 6 month old C57BL/6J mice and administered farnesol doses of 0.1, 1, and 10 mg/kg.
* The study found that farnesol-alone produces reward-related behavior in only male mice, while 1.0 mg/kg farnesol enhances locomotor activity in both male and female mice.
* The study used whole-cell patch-clamp electrophysiology and confocal microscopy to investigate changes in putative dopamine and GABA neurons.
* The study found that farnesol treatment increases VTA dopamine neuron firing frequency and upregulates α6* nAChRs in male mice.
* The study also found that farnesol treatment produces a significant decrease in inhibitory tone from GABA neurons.
* The study used a β2* nAChR antagonist, Dh βE, to determine if farnesol-induced conditioned place preference may be mediated through nAChRs.
* The study found that farnesol significantly increases nicotine-reward related behavior in male mice.

Main Message:
The study suggests that popular tobacco flavorants, such as farnesol, may alter smoking-related behavior and promote the need to examine additional ENDS flavors. The findings highlight the importance of understanding how other flavors, besides menthol, influence smoking behavior and the need for further research on the effects of farnesol and other flavorants on neurobiology. The study also emphasizes the need to increase our understanding of tobacco flavors' effects on public health, particularly in light of the growing use of flavored e-cigarettes among youth and adults.

Avelar AJ, Akers AT, Baumgard ZJ, Cooper SY, Casinelli GP, Henderson BJ. Why flavored vape products may be attractive: Green apple tobacco flavor elicits reward-related behavior, upregulates nAChRs on VTA dopamine neurons, and alters midbrain dopamine and GABA neuron function. Neuropharmacology. 2019;158:107729. doi:10.1016/j.neuropharm.2019.107729