电子烟的使用导致显著的β2-烟碱型乙酰胆碱受体占据：来自 PET 成像研究的证据。
Use of Electronic Cigarettes Leads to Significant Beta2-Nicotinic Acetylcholine Receptor Occupancy: Evidence From a PET Imaging Study.
机构信息
Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT.
PET center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
出版信息
Nicotine Tob Res. 2018 Mar 6;20(4):425-433. doi: 10.1093/ntr/ntx091.
BACKGROUND
Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain β2*-nicotinic acetylcholine receptors (β2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes.
METHODS
Seven nicotine users participated in positron emission tomography (PET) studies with (-)-[18F]Flubatine before and after nicotine challenge with 0, 8, and 36 mg/ml nicotine in a 3.3 Volt, 1.5 Ohm EC or a standard tobacco cigarette. Craving was evaluated before and after product use.
RESULTS
Average β2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared to 8 mg/ml EC at trend level. Average β2*-nAChR occupancy after tobacco cigarette smoking was 68 ± 18% and was not different compared with 8 mg/ml (64 ± 17%,) or 36 mg/ml (84 ± 3%) nicotine in EC users. Area under the curve (AUC) of blood nicotine level was higher in the cigarette smoking group compared with the 8mg/ml group (p = 0.03), but similar compared with the 36 mg/ml EC (p = 0.29). Drug craving was reduced after use of the tobacco cigarette, 8 mg/ml EC, and 36 mg/ml EC.
CONCLUSIONS
In this novel investigation of EC effects at β2*-nAChRs, we show that average β2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared with 8 mg/ml EC. Receptor occupancy and arterial blood nicotine levels after cigarette smoking were similar to 36 mg/ml EC use under controlled conditions. These findings suggest that the ECs studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers.
IMPLICATIONS
This is the first study to directly determine the neurologic effects of electronic cigarettes on human brain beta-2 nicotinic acetylcholine receptors using PET neuroimaging with (-)-[18F]Flubatine, a novel radiotracer. Our findings suggest that the e-cigarettes studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers.
背景
电子烟可通过气溶胶化尼古丁影响尼古丁成瘾。我们研究了电子烟中的尼古丁是否能传递到大脑β2*-烟碱型乙酰胆碱受体（β2*-nAChR），以及这与吸烟和香烟中尼古丁传递的行为效应有何关联。
方法
7 名尼古丁使用者参与了正电子发射断层扫描（PET）研究，在使用 3.3 伏、1.5 欧姆的 EC 或标准烟草香烟以 0、8 和 36 mg/ml 尼古丁进行尼古丁挑战前后，使用了（-）-[18F]Flubatine。在使用产品前后评估了渴望程度。
结果
在 EC 挑战 36 mg/ml 后，β2*-nAChR 占有率的平均值高于趋势水平的 8 mg/ml EC。在烟草香烟使用者中，吸烟后β2*-nAChR 占有率为 68±18%，与 8 mg/ml（64±17%）或 36 mg/ml EC（84±3%）尼古丁无差异。与 8 mg/ml 组相比，吸烟组的血尼古丁水平 AUC 更高（p=0.03），但与 36 mg/ml EC 组相比无差异（p=0.29）。使用烟草香烟、8 mg/ml EC 和 36 mg/ml EC 后，药物渴望均降低。
结论
在这项关于 EC 对β2*-nAChR 影响的新研究中，我们表明 36 mg/ml EC 挑战后的β2*-nAChR 占有率高于 8 mg/ml EC。在受控条件下，吸烟后受体占有率和动脉血尼古丁水平与 36 mg/ml EC 相似。这些发现表明，这里研究的电子烟具有滥用潜力，可能为吸烟人群提供了一种适当的尼古丁替代传递系统。
意义
这是第一项使用正电子发射断层扫描（PET）神经影像学技术，使用新型示踪剂（-）-[18F]Flubatine，直接确定电子烟对人类大脑β-2 烟碱型乙酰胆碱受体影响的研究。我们的发现表明，这里研究的电子烟具有滥用潜力，可能为吸烟人群提供了一种适当的尼古丁替代传递系统。
Zotero 插件