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The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice

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Abstract

The exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurable and rewarding effects. To test this hypothesis, male mice were selected with different nicotine metabolic rates that closely resembled in the smoker group. We evaluated their nicotine dependence and rewarding effects through conditioned place preference and withdrawal symptom tests, supplemented with dopamine release measurements. In both animal and human, the slow metabolism group (SMG) required less nicotine to maintain a comparable level of dependence than the fast metabolism group (FMG). The SMG could achieve similar rewarding effects to FMG despite consuming less nicotine. Comparable dopamine levels released were therefore critical in setting the nicotine acquisition behavior in this animal model and also for the smokers tested. Our findings suggested that even within the same ethnicity of established smokers (Chinese Han), differences in nicotine metabolism were an important parameter to modulate the degree of nicotine dependence.

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Data Availability

Data in this study are available on request from the corresponding authors.

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Funding

This work was supported by the Provincial and Ministerial Major Project of China (Grant Nos. 110202001031(JY-14), 110202102014, and 552022AK0070).

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Authors and Affiliations

  1. China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450000, China

    Mingda Liu, Hongjuan Wang, Yaning Fu, Xiangyu Li, Guanglin Liu, Ruiyan Wang, Yuan Zhang, Huan Chen, Hongwei Hou & Qingyuan Hu

  2. Key Laboratory of Tobacco Biological Effects, Zhengzhou, 450000, China

    Mingda Liu, Hongjuan Wang, Yaning Fu, Xiangyu Li, Guanglin Liu, Ruiyan Wang, Yuan Zhang, Huan Chen, Hongwei Hou & Qingyuan Hu

  3. Beijing Life Science Academy, Beijing, 100000, China

    Mingda Liu, Hongjuan Wang, Yaning Fu, Xiangyu Li, Guanglin Liu, Ruiyan Wang, Yuan Zhang, Huan Chen, Hongwei Hou & Qingyuan Hu

  4. Key Laboratory of Tobacco Biological Effects and Biosynthesis, Beijing, 100000, China

    Mingda Liu, Hongjuan Wang, Yaning Fu, Xiangyu Li, Guanglin Liu, Ruiyan Wang, Yuan Zhang, Huan Chen, Hongwei Hou & Qingyuan Hu

  5. National Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence, Beijing, China

    Ping Wu

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  1. Mingda Liu
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Contributions

M.L., H.W., Y.F., X.L., H.C., H.H., and Q.H. conceived and designed the experiments. M.L. performed the main experiments and data analysis and wrote the original draft. H.W. and Y.F. performed the population experiments. Y.Z. performed the nicotine and cotinine level detection experiments. G.L. and R.W. participated in assisting the dopamine release level detection. M.L., P.W., and H.C. revised the manuscript. H.C. and H.H. performed funding acquisition and supervision. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Huan Chen or Hongwei Hou.

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Ethical Approval

Ethical approval of human study was from Zhengzhou University.

Ethics committee of Drug Clinical Trials (Approval Number: 2021–06-01). All the animal procedures were approved by the Laboratory Animal Management and Ethics Committee of China National Tobacco Quality Supervision and Test Center (Approval Number: CTQTC-SYXK-2021002).

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Informed consent was obtained from all individual participants and authors involved in this study.

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Liu, M., Wang, H., Fu, Y. et al. The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04040-8

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