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Infralimbic Endothelin1 Is Critical for the Modulation of Anxiety-Like Behaviors

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Abstract

Endothelin1 (ET1) is a potent vasoconstrictor that is also known to be a neuropeptide that is involved in neural circuits. We examined the role of ET1 that has been implicated in the anxiogenic process. We found that infusing ET1 into the IL cortex increased anxiety-like behaviors. The ETA receptor (ETAR) antagonist (BQ123) but not the ETB receptor (ETBR) antagonist (BQ788) alleviated ET1-induced anxiety. ET1 had no effect on GABAergic neurotransmission or NMDA receptor (NMDAR)-mediated neurotransmission, but increased AMPA receptor (AMPAR)-mediated excitatory synaptic transmission. The changes in AMPAR-mediated excitatory postsynaptic currents were due to presynaptic mechanisms. Finally, we found that the AMPAR antagonists (CNQX) and BQ123 reversed ET1’s anxiogenic effect, with parallel and corresponding electrophysiological changes. Moreover, infusing CNQX + BQ123 into the IL had no additional anxiolytic effect compared to CNQX treatment alone. Altogether, our findings establish a previously unknown anxiogenic action of ET1 in the IL cortex. AMPAR-mediated glutamatergic neurotransmission may underlie the mechanism of ET1-ETAR signaling pathway in the regulation of anxiety.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (81200119, 81130079, 91232302, 81200863), a grant from the Fundamental Research Funds for the Central Universities (2015TS126), a grant from the Fundamental Research Funds for the Central Universities (121007), a grant from the China Postdoctoral Science Foundation Grant (2014 M552046), and a grant from Postdoctoral Science Foundation of Huazhong University of Science and Technology (2014).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Lin-Lin Bi, Lei Pei, Shu Shu, Hui-Juan Jin, Hong-Lin Yan, Na Wei, Shan Wang, Xin Yang, Huan-Huan Yan, Meng-meng Xu, Cheng-Ye Yao, Na Li, Na Tang, Jian-Hua Wu, Hou-Ze Zhu, Hao Li, You Cai, Yu Guo, Yan Shi, Qing Tian, Ling-Qiang Zhu & You-Ming Lu

  2. Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China

    Lin-Lin Bi, Lei Pei, Shu Shu, Hui-Juan Jin, Hong-Lin Yan, Na Wei, Shan Wang, Xin Yang, Huan-Huan Yan, Meng-meng Xu, Cheng-Ye Yao, Na Li, Na Tang, Jian-Hua Wu, Hou-Ze Zhu, Hao Li, You Cai, Yu Guo, Yan Shi, Qing Tian, Ling-Qiang Zhu & You-Ming Lu

  3. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Ming Chen

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  1. Lin-Lin Bi
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Bi, LL., Chen, M., Pei, L. et al. Infralimbic Endothelin1 Is Critical for the Modulation of Anxiety-Like Behaviors. Mol Neurobiol 53, 2054–2064 (2016). https://doi.org/10.1007/s12035-015-9163-9

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