This study aimed to investigate the impact of tobacco flavoring on oral nicotine consumption in mice using the two-bottle choice (2BC) test and assessed the potential impact of age and sex in their interactions.
Adolescent and adult male and female C57BL/6J mice were used. First, voluntary consumption of tobacco flavor concentrate from a commercial electronic cigarette liquid vendor (Avail Vapor LLC) was measured; then, the effects of tobacco flavoring in combination with nicotine were examined. In one approach, tobacco flavor concentration was kept constant while nicotine concentration varied, and in the second, nicotine was kept constant while the tobacco flavor concentration varied. Overall, tobacco flavoring decreased oral nicotine consumption in mice, and its effects were sex- and age-dependent. Although females consumed the tobacco-flavored solution at a slightly higher rate than males, male mice were more sensitive to the effects of the combination (nicotine + tobacco). Furthermore, adolescent mice showed a starker reduction in nicotine consumption in the presence of tobacco flavoring compared to adult mice. This attenuation was most likely due to a basal aversion to the tobacco flavoring itself, thus, creating a negative synergistic effect with nicotine. The study concluded that tobacco flavoring increases aversion to nicotine in the 2BC test in C57BL6J mice, suggesting that some flavors may diminish rather than enhance oral nicotine consumption in rodents. (Publisher abstract provided)