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7,8-Dihydroxyflavone Alleviates Anxiety-Like Behavior Induced by Chronic Alcohol Exposure in Mice Involving Tropomyosin-Related Kinase B in the Amygdala

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Abstract

Alcohol use–associated disorders are highly comorbid with anxiety disorders; however, their mechanism remains unknown. The amygdala plays a central role in anxiety. We recently found that 7,8-dihydroxyflavone (7,8-DHF) significantly reduces withdrawal symptoms in a rat model of chronic intermittent alcohol (ethanol) exposure. This study aimed to determine the role of 7,8-DHF in regulating anxiety induced by chronic alcohol exposure and its associated underlying mechanism. Male C57BL/6J mice were exposed to chronic intermittent alcohol for 3 weeks followed by alcohol withdrawal for 12 h with or without 7,8-DHF administered intraperitoneally. All mice were tested using an open field test and elevated plus maze to assess anxiety-like behaviors. Synaptic activity and intrinsic excitability in basal and lateral amygdala (BLA) neurons were assessed using electrophysiological recordings. 7,8-DHF alleviated alcohol-induced anxiety-like behavior and attenuated alcohol-induced enhancement of activities in BLA pyramidal neurons. Furthermore, 7,8-DHF prevented alcohol withdrawal–evoked augmentation of glutamatergic transmission in the amygdala and had no effect on GABAergic transmission in the amygdala, as demonstrated by unaltered frequency and amplitude of spontaneous inhibitory postsynaptic currents. Microinjection of K252a, a tropomyosin-related kinase B (TrkB) antagonist, into the BLA blocked the effects of 7,8-DHF on anxiety-like behavior and neuronal activity in the BLA. Our findings suggest that 7,8-DHF alleviates alcohol-induced anxiety-like behavior induced by chronic alcohol exposure through regulation of glutamate transmission involving TrKB in the BLA.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgments

We would like to thank Professor Bing-Xing Pan for technical assistance.

Funding

This study was supported by the National Key R&D Program of China (2018YFC1314404 to XFZ) and grants from the National Science Foundation of China (NSFC) (81871041, 81371463 to YZG); Heilongjiang Science Project (H2017076, Y.Z.G.); Graduate Innovative Research Programs of Mudanjiang Medical University, China (Nos. 2018YJSCX-01MY, 2019YJSCX-04MY, YZG).

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  1. Department of Physiology & Neurobiology, Mudanjiang Medical University, Mudanjiang, 157011, China

    Na Wang, Xing Liu, Xin-Xin Li, Wei Ma, Yan-Min Xu, Yong Liu, Qing Gao, Tao Yang, Xiao-Feng Zhu & Yan-Zhong Guan

  2. Department of Neurology, The Affiliated First Hospital of Jiamusi University, Jiamusi, 154000, China

    Xin-Tong Li

  3. Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510828, China

    Hongxuan Wang & Ying Peng

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  1. Na Wang
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Contributions

YZG conceived the project; NW, XXL, YL, TY, and QG performed the experiments; YMX, WM, XTL collected data; NW, YP, and XL analyzed the data; XFZ and YZG supervised the project; NW, WM, HXW, and YZG wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiao-Feng Zhu or Yan-Zhong Guan.

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All experiments were conducted according to the guidelines and protocols for rodent experimentation approved by the Institutional Animal Care and Use Committee of Mudanjiang Medical University.

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Wang, N., Liu, X., Li, XT. et al. 7,8-Dihydroxyflavone Alleviates Anxiety-Like Behavior Induced by Chronic Alcohol Exposure in Mice Involving Tropomyosin-Related Kinase B in the Amygdala. Mol Neurobiol 58, 92–105 (2021). https://doi.org/10.1007/s12035-020-02111-0

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