Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
Nutrients. 2024 Sep 10;16(18):3048. doi: 10.3390/nu16183048.
Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.
尼古丁依赖是大多数吸烟者过度暴露于烟草燃烧化合物的重要原因。尼古丁替代疗法是治疗尼古丁依赖的主要方法，但仍存在其缺点，如无法缓解戒断效应和适用范围有限。有人假设，低剂量尼古丁和咖啡因的组合可以达到与高剂量尼古丁相同的心理刺激效果，而不会引起尼古丁戒断效应。为了建立尼古丁依赖模型，雄性 C57BL/6J 小鼠每天皮下注射尼古丁（2mg/kg）4 次，同时给予含有尼古丁的水。它们被随机分为四组。戒断 24 小时后，不同组分别注射生理盐水、尼古丁（0.25mg/kg 或 0.1mg/kg）或尼古丁（0.1mg/kg）和咖啡因（20mg/kg）。通过评估体征、旷场试验、高架十字迷宫实验、强迫游泳试验、热板试验和新物体识别试验来评估行为和生理变化。使用 ELISA 分析中脑前额叶皮层（PFC）和腹侧被盖区（VTA）中多巴胺释放的变化。结果表明，咖啡因和尼古丁的组合可以有效缓解尼古丁戒断综合征，提高运动能力和疼痛阈值，减轻焦虑和抑郁，增强记忆和认知能力，并增加 PFC 和 VTA 中多巴胺的释放。因此，咖啡因与尼古丁联合使用具有成为稳定有效的戒烟治疗选择的潜力。
