Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Drug Alcohol Depend. 2020 Jun 1;211:107995. doi: 10.1016/j.drugalcdep.2020.107995. Epub 2020 Apr 25.
The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion.
Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine.
Mice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone.
Our data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.
在过去的十年中，电子烟的使用有所增加。为了确定电子烟液（e-juice）的滥用倾向与尼古丁本身有何不同，以及确定口味的影响，我们比较了含尼古丁的水果味和烟草味电子烟液及其不含尼古丁的版本与尼古丁单独在小鼠口服、奖励和厌恶模型中的作用。
成年雄性 C57BL/6J 小鼠自愿消耗口服尼古丁、与水果味和烟草味电子烟液等效的尼古丁浓度，以及与其尼古丁含量相同的无尼古丁版本的电子烟液，在双瓶选择测试中进行比较。通过外周给予电子烟液或尼古丁评估条件性位置偏好和厌恶。在皮下注射电子烟液或尼古丁后测量血清尼古丁和可替宁水平。
与单独使用尼古丁相比，小鼠对水果味电子烟液的消耗和偏好更高。这种增加不是由于口味本身引起的，因为只有在测试的最高浓度下，无尼古丁的水果味电子烟液的消耗才会增加。烟草味电子烟液没有观察到这种增加的消耗和偏好。电子烟液的水果味的条件性位置偏好、厌恶和尼古丁药代动力学与单独使用尼古丁没有显著差异。
我们的数据表明，与单独使用尼古丁相比，水果味而不是烟草味增加了电子烟液的口服消耗。此外，这种增强不是由于增加了对风味本身的消耗、外周给药后改变了奖赏或厌恶特性，或改变了药代动力学。这种特定于风味的增强表明，与单独使用尼古丁相比，某些口味可能会导致更高的尼古丁摄入和电子烟液的使用增加。
