1. Academic Validation
  2. Harmane Potentiates Nicotine Reinforcement Through MAO-A Inhibition at the Dose Related to Cigarette Smoking

Harmane Potentiates Nicotine Reinforcement Through MAO-A Inhibition at the Dose Related to Cigarette Smoking

  • Front Mol Neurosci. 2022 Jun 27;15:925272. doi: 10.3389/fnmol.2022.925272.
Zheng Ding 1 2 3 Xiangyu Li 1 2 3 Huan Chen 1 2 3 Hongwei Hou 1 2 3 Qingyuan Hu 1 2 3
Affiliations

Affiliations

  • 1 China National Tobacco Quality Supervision & Test Center, Zhengzhou, China.
  • 2 Key Laboratory of Tobacco Biological Effects, Zhengzhou, China.
  • 3 Joint Laboratory of Translational Neurobiology, Zhengzhou, China.
Abstract

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.

Keywords

cigarette smoking; dopamine; harmane; monoamine oxidase (MAO); nicotine; substance abuse.

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