title: Infralimbic Endothelin1 Is Critical for the Modulation of Anxiety-Like Behaviors.
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 ET(A) receptor (ET(A)R) antagonist (BQ123) but not the ET(B) receptor (ET(B)R) 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-ET(A)R signaling pathway in the regulation of anxiety.
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. linlinbi2013@163.com.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China. linlinbi2013@163.com.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bi
authors.affiliation: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Pei
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Shu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Yan
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Yan
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cheng-Ye
authors.initials: CY
authors.lastname: Yao
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tang
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hou-Ze
authors.initials: HZ
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: You
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling-Qiang
authors.initials: LQ
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Neurological Diseases of Ministry of Education, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. lym@hust.edu.cn.|Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, China. lym@hust.edu.cn.
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Lu
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D001522:Behavior, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D018091:Receptors, AMPA / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D010456:Peptides, Cyclic; D018091:Receptors, AMPA; D017466:Receptors, Endothelin; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: AMPAR; Anxiety; ET1; ETA receptor; Infralimbic cortex; Mice