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Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice

Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use d...

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Autores principales: Bai, Xiaohui, Zhang, Kun, Ou, Chaopeng, Nie, Bilin, Zhang, Jianxing, Huang, Yongtian, Zhang, Yingjun, Huang, Jingxiu, Ouyang, Handong, Cao, Minghui, Huang, Wan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352381/
https://www.ncbi.nlm.nih.gov/pubmed/37460788
http://dx.doi.org/10.1038/s42003-023-05106-4
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author Bai, Xiaohui
Zhang, Kun
Ou, Chaopeng
Nie, Bilin
Zhang, Jianxing
Huang, Yongtian
Zhang, Yingjun
Huang, Jingxiu
Ouyang, Handong
Cao, Minghui
Huang, Wan
author_facet Bai, Xiaohui
Zhang, Kun
Ou, Chaopeng
Nie, Bilin
Zhang, Jianxing
Huang, Yongtian
Zhang, Yingjun
Huang, Jingxiu
Ouyang, Handong
Cao, Minghui
Huang, Wan
author_sort Bai, Xiaohui
collection PubMed
description Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150(flox/flox) mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response.
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spelling pubmed-103523812023-07-19 Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice Bai, Xiaohui Zhang, Kun Ou, Chaopeng Nie, Bilin Zhang, Jianxing Huang, Yongtian Zhang, Yingjun Huang, Jingxiu Ouyang, Handong Cao, Minghui Huang, Wan Commun Biol Article Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal. However, activating or inhibiting glutamatergic neurons, or activating GABAergic neurons cannot affect or alter CPA response. AKAP150 protein expression and phosphorylated TRPV1 (p-TRPV1) were significantly upregulated in these two CPA models. In AKAP150(flox/flox) mice and C57/B6J wild-type mice, cell-type-selective inhibition of AKAP150 in GABAergic neurons in the vlPAG attenuated aversion. However, downregulating AKAP150 in glutamatergic neurons did not attenuate aversion. Knockdown of AKAP150 in GABAergic neurons effectively reversed the p-TRPV1 upregulation in these two CPA models utilized in our study. Collectively, inhibition of the AKAP150/p-TRPV1 pathway in GABAergic neurons in the vlPAG may be considered a potential therapeutic target for the CPA response. Nature Publishing Group UK 2023-07-17 /pmc/articles/PMC10352381/ /pubmed/37460788 http://dx.doi.org/10.1038/s42003-023-05106-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bai, Xiaohui
Zhang, Kun
Ou, Chaopeng
Nie, Bilin
Zhang, Jianxing
Huang, Yongtian
Zhang, Yingjun
Huang, Jingxiu
Ouyang, Handong
Cao, Minghui
Huang, Wan
Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title_full Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title_fullStr Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title_full_unstemmed Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title_short Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice
title_sort selective activation of akap150/trpv1 in ventrolateral periaqueductal gray gabaergic neurons facilitates conditioned place aversion in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352381/
https://www.ncbi.nlm.nih.gov/pubmed/37460788
http://dx.doi.org/10.1038/s42003-023-05106-4
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