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

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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… Click to show full 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: harmane; mao inhibition; cigarette smoking; cigarette; dose related

Journal Title: Frontiers in Molecular Neuroscience
Year Published: 2022

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