Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Department of Biomedical Sciences, Marshall University, Joan C Edwards School of Medicine, Huntington, WV, USA.
Neuropsychopharmacology. 2017 Nov;42(12):2285-2291. doi: 10.1038/npp.2017.72. Epub 2017 Apr 2.
Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.
要理解为什么薄荷醇香烟的吸烟者戒烟率低于非薄荷醇吸烟者，就需要确定尼古丁、薄荷醇和乙酰胆碱改变的神经元。腹侧被盖区（VTA）中的多巴胺能（DA）神经元介导尼古丁的正强化作用。使用小鼠模型，我们表明薄荷醇增强了烟碱型乙酰胆碱受体（nAChR）在中脑 DA 神经元上的尼古丁诱导变化。薄荷醇加尼古丁比单独尼古丁上调 nAChR 数量和功能更多。薄荷醇还增强了尼古丁诱导的中脑 DA 神经元兴奋性的变化。在条件性位置偏好（CPP）测定中，我们观察到薄荷醇加尼古丁比单独尼古丁产生更强的与奖赏相关的行为。我们的结果将中脑 DA 神经元的变化与薄荷醇诱导的尼古丁奖赏相关行为的增强联系起来，这可能有助于解释为什么薄荷醇香烟的吸烟者戒烟率降低。
