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Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice

Exacerbated attack behavior has a profound socioeconomic impact and devastating social consequences; however, there is no satisfactory clinical management available for an escalated attack behavior. Social isolation (SI) is widespread during this pandemic and may exert detrimental effects on mental...

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Autores principales: Fang, Weiqing, Wang, Xiaorong, Cai, Miao, Liu, Xinxin, Wang, Xuemeng, Lu, Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322622/
https://www.ncbi.nlm.nih.gov/pubmed/34335265
http://dx.doi.org/10.3389/fphar.2021.700003
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author Fang, Weiqing
Wang, Xiaorong
Cai, Miao
Liu, Xinxin
Wang, Xuemeng
Lu, Wen
author_facet Fang, Weiqing
Wang, Xiaorong
Cai, Miao
Liu, Xinxin
Wang, Xuemeng
Lu, Wen
author_sort Fang, Weiqing
collection PubMed
description Exacerbated attack behavior has a profound socioeconomic impact and devastating social consequences; however, there is no satisfactory clinical management available for an escalated attack behavior. Social isolation (SI) is widespread during this pandemic and may exert detrimental effects on mental health, such as causing heightened attack behavior. To explore the therapeutic approaches that alleviate the SI-induced heightened attack behavior, we utilized pharmacological methods targeting the GluN2B/NO signaling pathway during the attack behavior. Ifenprodil and TAT-9C peptide targeting GluN2B showed that the inhibition of GluN2B mitigated the SI-induced escalated attack behavior and the SI-induced aberrant nitric oxide (NO) level in the brain. Additionally, the potentiation of the NO level by L-arginine reversed the effects of the inhibition of GluN2B. Moreover, we showed that high doses of L-NAME and 7-NI and subeffective doses of L-NAME in combination with ifenprodil or TAT-9C or subeffective doses of 7-NI plus ifenprodil or TAT-9C all decreased the SI-induced escalated attack behavior and reduced the NO level, further supporting the idea that GluN2B/NO signaling is a crucial modulator of the escalated attack behavior.
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spelling pubmed-83226222021-07-31 Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice Fang, Weiqing Wang, Xiaorong Cai, Miao Liu, Xinxin Wang, Xuemeng Lu, Wen Front Pharmacol Pharmacology Exacerbated attack behavior has a profound socioeconomic impact and devastating social consequences; however, there is no satisfactory clinical management available for an escalated attack behavior. Social isolation (SI) is widespread during this pandemic and may exert detrimental effects on mental health, such as causing heightened attack behavior. To explore the therapeutic approaches that alleviate the SI-induced heightened attack behavior, we utilized pharmacological methods targeting the GluN2B/NO signaling pathway during the attack behavior. Ifenprodil and TAT-9C peptide targeting GluN2B showed that the inhibition of GluN2B mitigated the SI-induced escalated attack behavior and the SI-induced aberrant nitric oxide (NO) level in the brain. Additionally, the potentiation of the NO level by L-arginine reversed the effects of the inhibition of GluN2B. Moreover, we showed that high doses of L-NAME and 7-NI and subeffective doses of L-NAME in combination with ifenprodil or TAT-9C or subeffective doses of 7-NI plus ifenprodil or TAT-9C all decreased the SI-induced escalated attack behavior and reduced the NO level, further supporting the idea that GluN2B/NO signaling is a crucial modulator of the escalated attack behavior. Frontiers Media S.A. 2021-07-16 /pmc/articles/PMC8322622/ /pubmed/34335265 http://dx.doi.org/10.3389/fphar.2021.700003 Text en Copyright © 2021 Fang, Wang, Cai, Liu, Wang and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Fang, Weiqing
Wang, Xiaorong
Cai, Miao
Liu, Xinxin
Wang, Xuemeng
Lu, Wen
Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title_full Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title_fullStr Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title_full_unstemmed Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title_short Targeting GluN2B/NO Pathway Ameliorates Social Isolation–Induced Exacerbated Attack Behavior in Mice
title_sort targeting glun2b/no pathway ameliorates social isolation–induced exacerbated attack behavior in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322622/
https://www.ncbi.nlm.nih.gov/pubmed/34335265
http://dx.doi.org/10.3389/fphar.2021.700003
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