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Anxiolytic Actions of Motilin in the Basolateral Amygdala

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Abstract

Motilin is a 22-amino-acid gastrointestinal polypeptide that was first isolated from the porcine intestine. We identified that motilin receptor is highly expressed in GABAergic interneurons in the basolateral nucleus (BLA) of the amygdala, the structure of which is closely involved in assigning stress disorder and anxiety. However, little is known about the role of motilin in BLA neuronal circuits and the molecular mechanisms of stress-related anxiety. Whole-cell recordings from amygdala slices showed that motilin depolarized the interneurons and facilitated GABAergic transmission in the BLA, which is mimicked by the motilin receptor agonist, erythromycin. BLA local injection of erythromycin or motilin can reduce the anxiety-like behavior in mice after acute stress. Therefore, motilin is essential in regulating interneuron excitability and GABAergic transmission in BLA. Moreover, the anxiolytic actions of motilin can partly be explained by modulating the BLA neuronal circuits. The present data demonstrate the importance of motilin in anxiety and the development of motilin receptor non-peptide agonist as a clear target for the potential treatment of anxiety disorders.

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Acknowledgments

We kindly thank Chugai Pharmaceutical Co., Ltd. (Japan) for the gift of the motilin receptor antagonist MA-2029. This work was supported by National Natural Science Foundation of China No. 31070923 and 31271144.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi’an, 710032, China

    Bin Feng, Jun Zhang, Yan-yan Guo, Xiao-qiang Li & Ming-gao Zhao

  2. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China

    Jin-cheng Liu & Ding-hua Yi

  3. R&D Portfolio Management Department, Chugai Pharmaceutical Co., Ltd., Chuo-ku, Tokyo, 103-8324, Japan

    Ken-ichi Ozaki

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  1. Bin Feng
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  2. Jin-cheng Liu
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Correspondence to Xiao-qiang Li or Ming-gao Zhao.

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Bin Feng, Jin-cheng Liu, and Jun Zhang contributed equally to this work.

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Feng, B., Liu, Jc., Zhang, J. et al. Anxiolytic Actions of Motilin in the Basolateral Amygdala. Mol Neurobiol 47, 892–902 (2013). https://doi.org/10.1007/s12035-012-8383-5

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