Ding Zheng, Li Xiangyu, Chen Huan, Hou Hongwei, Hu Qingyuan
China National Tobacco Quality Supervision & Test Center, Zhengzhou, China.
Key Laboratory of Tobacco Biological Effects, Zhengzhou, China.
Front Mol Neurosci. 2022 Jun 27;15:925272. doi: 10.3389/fnmol.2022.925272. eCollection 2022.
Nicotine is the primary addictive component in cigarette smoke, and dopamine release induced by nicotine is considered a significant cause of persistent smoking and nicotine dependence. However, the effects of nicotine replacement therapy on smoking cessation were less effective than expected, suggesting that other non-nicotine constituents may potentiate the reinforcing effects of nicotine. Harmane is a potent, selective monoamine oxidase A (MAO-A) inhibitor found in cigarette smoke, but showed no effect on nicotine self-administration in previous studies, possibly due to the surprisingly high doses used. In the present study, we found that harmane potentiated nicotine self-administration on the fixed ration schedule at the dose related to human cigarette smoking by the synergistic effects in up-regulating genes in addiction-related pathways, and the effect was reduced at doses 10 times higher or lower than the smoking-related dose. The smoking-related dose of harmane also enhanced the increase of locomotor activity induced by nicotine, accompanied by increased dopamine basal level and dopamine release in the nucleus accumbens through MAO-A inhibition. Our findings provided new evidence for the important role of non-nicotine ingredients of tobacco products in smoking addiction.
尼古丁是香烟烟雾中的主要成瘾成分，尼古丁诱导的多巴胺释放被认为是持续吸烟和尼古丁依赖的重要原因。然而，尼古丁替代疗法对戒烟的效果不如预期，这表明其他非尼古丁成分可能增强了尼古丁的强化作用。哈尔满是在香烟烟雾中发现的一种强效、选择性单胺氧化酶A（MAO-A）抑制剂，但在先前的研究中对尼古丁自我给药没有影响，这可能是由于使用的剂量高得出奇。在本研究中，我们发现哈尔满通过上调成瘾相关途径中的基因的协同作用，在与人类吸烟相关的剂量下，增强了固定比率给药方案下的尼古丁自我给药，并且在高于或低于吸烟相关剂量10倍的剂量下，这种作用减弱。与吸烟相关剂量的哈尔满还增强了尼古丁诱导的运动活动增加，同时通过抑制MAO-A导致伏隔核中多巴胺基础水平和多巴胺释放增加。我们的研究结果为烟草制品中的非尼古丁成分在吸烟成瘾中的重要作用提供了新证据。
