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L-menthol exhibits antidepressive-like effects mediated by the modification of 5-HTergic, GABAergic and DAergic systems

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Abstract

Major depression disorder, also known as depression, with a significant and persistent low mood as the main clinical features, is the main type of mood disorders. L-menthol (LM), the main active ingredient of mint, has been considered as safe and healthy natural ingredient by the Food and Drug Administration in the USA. In this study, LM (40 mg/kg, i.g.) produced antidepressant-like effect in the forced swimming test (FST) in mice. The sub-effective dose (5 mg/kg, i.g.) of LM combined with the sub-effective dose of fluoxetine (5 mg/kg, i.p.) or reboxetine (2.5 mg/kg, i.p.) could significantly shorten the immobility time in the FST. Pretreatment with ondansetron (a highly selective 5-HT3 receptor antagonist, 8 mg/kg, i.p.), bicuculline [a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.] and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) significantly reversed the antidepressant-like effect of LM (40 mg/kg, i.g.). In contrast, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and N-methyl-d-aspartic acid (an agonist at the glutamate site, 75 mg/kg, i.p.) did not eliminate the antidepressant-like effect of LM. All of these above indicated that LM is able to induce an antidepressant-like effect mediated by the modification of 5-HTergic, GABAergic and DAergic systems in the FST. LM might be used as combination therapy in depressed patients and is a potential antidepressant.

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Acknowledgements

The authors are grateful for the National key R&D program (Grant No. 2016YFC0500303), the Special Fund for Agro-scientific Research in the Public Interest (Grant No. 201303111), and Jilin Province Science and Technology Development Program (Grant Nos. 20160307005YY, 20150307012YY).

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  1. Weidong Wang, Yuanyuan Jiang, Enbo Cai and Bingchen Li have contributed equally to this work.

Authors and Affiliations

  1. College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, Jilin, China

    Weidong Wang, Yuanyuan Jiang, Enbo Cai, Yan Zhao, Hongyan Zhu, Lianxue Zhang & Yugang Gao

  2. Antu Forestry Co., Ltd, Yanbian, 133600, Jilin, China

    Bingchen Li

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  1. Weidong Wang
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  2. Yuanyuan Jiang
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Correspondence to Yan Zhao or Yugang Gao.

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Wang, W., Jiang, Y., Cai, E. et al. L-menthol exhibits antidepressive-like effects mediated by the modification of 5-HTergic, GABAergic and DAergic systems. Cogn Neurodyn 13, 191–200 (2019). https://doi.org/10.1007/s11571-018-9513-1

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  • DOI: https://doi.org/10.1007/s11571-018-9513-1

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