Akinola Lois S, Buzzi Belle, Kalck Erin, Le Kimmie, Klein Sarah, Vaughn Julian, Basir Jamil, Poklis Justin, Whiteaker Paul, Shelton Keith L, Damaj M Imad
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Neuropharmacology. 2025 May 1;268:110315. doi: 10.1016/j.neuropharm.2025.110315. Epub 2025 Jan 18.
Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine. Our studies show that male and female young adult mice respond to nicotine, demonstrating notable sex-related differences in intake, locomotor sensitization, and somatic withdrawal signs. In addition, we characterized intake in adolescent mice, showing sex differences as well. Finally, we showed genotype-related differences when using β2 knock-out mice, emphasizing the role of the β2 nAChR in nicotine reward and nicotine intake. This new model offers a more targeted approach to studying the potential risks of nicotine vaping in a more relevant and face-valid model compared to traditional whole-body nicotine vapor exposure in rodents.
在美国，吸烟仍然是可预防死亡的主要原因之一。尽管在过去几年中，可燃香烟的使用率有所下降，但电子尼古丁传送系统的普及率却持续上升。吸电子烟并非没有风险，其长期影响，尤其是对易感人群的影响，在很大程度上仍然未知。本研究引入了一种新型的、口鼻受限的尼古丁蒸汽自我给药小鼠模型，以研究尼古丁浓度、基因型、性别和年龄对自我给药以及对尼古丁行为反应的影响。我们的研究表明，年轻成年雄性和雌性小鼠对尼古丁有反应，在摄入量、运动致敏和躯体戒断症状方面表现出显著的性别差异。此外，我们还对青春期小鼠的摄入量进行了表征，也显示出性别差异。最后，我们在使用β2基因敲除小鼠时发现了基因型相关差异，强调了β2烟碱型乙酰胆碱受体在尼古丁奖赏和尼古丁摄入中的作用。与传统的啮齿动物全身尼古丁蒸汽暴露相比，这个新模型提供了一种更具针对性的方法，在一个更相关且表面效度高的模型中研究尼古丁电子烟的潜在风险。
