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The involvement of AMPA–ERK1/2–BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate

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Abstract

It was recently discovered that ketamine can relieve depression in a matter of hours through an action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This is much more rapid than the several weeks required for the available antidepressants to show therapeutic efficacy. However, ketamine has negative side effects. The aim of this study was to determine whether the natural prokinetic drug meranzin hydrate (MH) has a fast-acting antidepressant effect mediated by AMPA receptors. By means of in vivo and in vitro experiments, we found that (1) treatment of rats with MH at 9 mg/kg decreased immobility time in a forced swimming test (FST), as did the popular antidepressant fluoxetine and the AMPA receptor positive modulator aniracetam. Pretreatment of rats with NBQX (10 mg/kg), an antagonist of AMPA receptors, blocked this effect of MH. (2) MH increased number of crossings of forced swimming rats in the open field test. (3) FST enhanced hippocampal ERK1/2, p-ERK1/2 and BDNF expression levels. MH (9 mg/kg) treatment further up-regulated hippocampal p-ERK1/2 and BDNF expression levels, and this effect was prevented by NBQX. (4) MH-increased BDNF expression corresponded with MH-decreased immobility time in the FST. (5) In vitro experiments, we found that incubation of rats hippocampus slices with MH (10, 20 μM respectively) increased concentrations of BDNF and p-ERK1/2. This effect of MH (20 μM) were prevented by NBQX. In conclusion, in animals subjected to acute stress, the natural prokinetic drug MH produced a rapid effect mediated by AMPA receptors and involving BDNF modulation through the ERK1/2 pathway.

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Acknowledgments

This work was supported by a grant (No. 81072967; No.30572339; No.81173591) from Natural Foundation of our country, and partly supported by the fund from National Key Clinical Specialist vocational school of TCM encephalopathy and the Huge Project to Boost Chinese Drug Development (2011ZX09101-009-03). This work was also supported by the National Natural Science Foundation of our country (30801506).

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China

    Ying Xie, Xi Huang, Sui-yu Hu, Ying-jin Zhang, Yang Wang, Xin-jian Qiu, Ping Ren, Rong Fan, Chun-hu Zhang, Wei-bin Xie, Hui Ji & Juan He

  2. National Key Clinical Specialist vocational School of TCM Encephalopathy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

    Ying Xie, Xi Huang, Sui-yu Hu, Ying-jin Zhang, Yang Wang, Xin-jian Qiu, Ping Ren, Rong Fan, Chun-hu Zhang, Wei-bin Xie, Hui Ji & Juan He

  3. Key Unit of Traditional Chinese Medicine Gan of SATCM, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

    Ying Xie, Xi Huang, Sui-yu Hu, Ying-jin Zhang, Yang Wang, Xin-jian Qiu, Ping Ren, Rong Fan, Chun-hu Zhang, Wei-bin Xie, Hui Ji & Juan He

  4. Laboratory of TCM Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, People’s Republic of China

    Xi Huang, Zhao-qian Liu & Hong-hao Zhou

  5. Jiangxi Qingfeng Pharmaceutical Company Ltd, Ganzhou, 341000, People’s Republic of China

    Xiao Chen & Linhong Xie

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  1. Ying Xie
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Correspondence to Xi Huang.

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Xie, Y., Huang, X., Hu, Sy. et al. The involvement of AMPA–ERK1/2–BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate. Amino Acids 44, 413–422 (2013). https://doi.org/10.1007/s00726-012-1347-2

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  • DOI: https://doi.org/10.1007/s00726-012-1347-2

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