Swenson Sabrina M, Hill Sean P, Adeshina Dami, Hammers Gabrielle V, McSweeney Sydney M, Sword M Kyle, Grooms Matthew O, Maddox Sarah K, Strcula Hannah D, Olszewski Nathan A, Tetteh-Quarshie Samuel, Henderson Brandon J
Department of Biomedical Sciences, Joan C Edwards School of Medicine at Marshall University, Huntington, West Virginia.
Department of Biomedical Sciences, Joan C Edwards School of Medicine at Marshall University, Huntington, West Virginia.
J Pharmacol Exp Ther. 2025 Aug;392(8):103651. doi: 10.1016/j.jpet.2025.103651. Epub 2025 Jul 1.
Electronic nicotine delivery systems (ENDSs) are a unique from combustible cigarettes due to the availability of flavor options which make these devices more attractive. Prior preclinical investigations have determined that menthol and green apple flavorants can enhance nicotine reward and reinforcement by altering dopamine transmission via nicotinic acetylcholine receptor modulation in reward-mediating brain areas. In this study, we investigated the impact of vanilla (vanillin and ethyl vanillin) and cherry (ethyl vanillin, vanillin, ethyl acetate, ethyl maltol, and maltol) flavors on reinforcement-related behavior with and without nicotine. Male and female adolescent C57BL/6J mice were used in an e-Vape self-administration assay. Four combinations were shown to increase reinforcement-related behavior: nicotine plus menthol, nicotine plus cherry, nicotine plus vanilla, and vanilla alone. We observed that zero-nicotine cherry-flavored ENDSs did not produce robust reinforcement-related behavior when compared with control vapor. We observed that zero-nicotine vanilla-flavored ENDSs did produce reinforcement-related behavior in adolescent male and female mice; the addition of nicotine did not produce a significant difference in active nose pokes or deliveries but did have increased active-to-inactive ratio. Additionally, we found that vanilla alone was able to modulate tonic and phasic release of dopamine in the nucleus accumbens core. We also looked at the physical interactions of green apple and vanilla flavors on nicotinic subunits. These data provide additional evidence that some chemical flavors promote vaping-related behaviors without the inclusion of nicotine. SIGNIFICANCE STATEMENT: The e-Vape self-administration paradigm is a translationally relevant method of investigating the impact of different flavorants on nicotine use. Because most electronic nicotine delivery system users vape flavored nicotine products, it raises questions about how chemical flavorants alter nicotine addiction and if they increase abuse liability themselves. In accordance with our prior findings on green apple, vanilla flavorants are able to cause changes in reward-related behaviors in the absence of nicotine potentially through altering dopamine release in the nucleus accumbens.
电子尼古丁传送系统（ENDSs）与可燃香烟不同，因为有多种口味可供选择，这使得这些设备更具吸引力。先前的临床前研究已确定，薄荷醇和青苹果香料可通过调节奖励介导脑区中的烟碱型乙酰胆碱受体来改变多巴胺传递，从而增强尼古丁奖赏和强化作用。在本研究中，我们调查了香草味（香草醛和乙基香草醛）和樱桃味（乙基香草醛、香草醛、乙酸乙酯、乙基麦芽酚和麦芽酚）在有或没有尼古丁情况下对强化相关行为的影响。雄性和雌性青春期C57BL/6J小鼠用于电子雾化器自我给药试验。结果显示有四种组合会增加强化相关行为：尼古丁加薄荷醇、尼古丁加樱桃味、尼古丁加香草味以及单独的香草味。我们观察到，与对照蒸汽相比，零尼古丁樱桃味ENDSs不会产生强烈的强化相关行为。我们观察到，零尼古丁香草味ENDSs在青春期雄性和雌性小鼠中确实产生了强化相关行为；添加尼古丁后，主动鼻触或给药次数没有显著差异，但主动与非主动比率有所增加。此外，我们发现单独的香草味能够调节伏隔核核心区多巴胺的紧张性和相位性释放。我们还研究了青苹果味和香草味在烟碱亚基上的物理相互作用。这些数据提供了更多证据，表明某些化学香料在不添加尼古丁的情况下也会促进与雾化相关的行为。意义声明：电子雾化器自我给药范式是一种与转化研究相关的方法，用于研究不同香料对尼古丁使用的影响。由于大多数电子尼古丁传送系统使用者吸食有香味的尼古丁产品，这就引发了关于化学香料如何改变尼古丁成瘾以及它们自身是否会增加滥用可能性的问题。根据我们之前关于青苹果味的研究结果，香草味香料在没有尼古丁的情况下可能通过改变伏隔核中的多巴胺释放来引起与奖励相关行为的变化。
