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A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference

Drug relapse is a big clinical challenge in the treatment of addiction, but its neural circuit mechanism is far from being fully understood. Here, we identified a novel cholinergic pathway from choline acetyltransferase-positive neurons in the external lateral parabrachial nucleus (eLPB(ChAT)) to th...

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Autores principales: He, Teng, Chen, Wenwen, Fan, Yu, Xu, Xing, Guo, Hao, Li, Nanqin, Lu, Xue, Ge, Feifei, Guan, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536296/
https://www.ncbi.nlm.nih.gov/pubmed/36213311
http://dx.doi.org/10.1093/braincomms/fcac219
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author He, Teng
Chen, Wenwen
Fan, Yu
Xu, Xing
Guo, Hao
Li, Nanqin
Lu, Xue
Ge, Feifei
Guan, Xiaowei
author_facet He, Teng
Chen, Wenwen
Fan, Yu
Xu, Xing
Guo, Hao
Li, Nanqin
Lu, Xue
Ge, Feifei
Guan, Xiaowei
author_sort He, Teng
collection PubMed
description Drug relapse is a big clinical challenge in the treatment of addiction, but its neural circuit mechanism is far from being fully understood. Here, we identified a novel cholinergic pathway from choline acetyltransferase-positive neurons in the external lateral parabrachial nucleus (eLPB(ChAT)) to the GABAergic neurons in the central nucleus of the amygdala (CeA(GABA)) and explored its role in methamphetamine priming-induced reinstatement of conditioned place preference. The anatomical structure and functional innervation of the eLPB(ChAT)–CeA(GABA) pathway were investigated by various methods such as fluorescent micro-optical sectioning tomography, virus-based neural tracing, fibre photometry, patch-clamp and designer receptor exclusively activated by a designer drug. The role of the eLPB(ChAT)–CeA(GABA) pathway in methamphetamine relapse was assessed using methamphetamine priming-induced reinstatement of conditioned place preference behaviours in male mice. We found that the eLPB(ChAT) neurons mainly projected to the central nucleus of the amygdala. A chemogenetic activation of the eLPB(ChAT) neurons in vitro or in vivo triggered the excitabilities of the CeA(GABA) neurons, which is at least in part mediated via the cholinergic receptor system. Most importantly, the chemogenetic activation of either the eLPB(ChAT) neurons or the eLPB(ChAT) neurons that project onto the central nucleus of the amygdala decreased the methamphetamine priming-induced reinstatement of conditioned place preference in mice. Our findings revealed a previously undiscovered cholinergic pathway of the eLPB(ChAT)–CeA(GABA) and showed that the activation of this pathway decreased the methamphetamine priming-induced reinstatement of conditioned place preference.
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spelling pubmed-95362962022-10-07 A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference He, Teng Chen, Wenwen Fan, Yu Xu, Xing Guo, Hao Li, Nanqin Lu, Xue Ge, Feifei Guan, Xiaowei Brain Commun Original Article Drug relapse is a big clinical challenge in the treatment of addiction, but its neural circuit mechanism is far from being fully understood. Here, we identified a novel cholinergic pathway from choline acetyltransferase-positive neurons in the external lateral parabrachial nucleus (eLPB(ChAT)) to the GABAergic neurons in the central nucleus of the amygdala (CeA(GABA)) and explored its role in methamphetamine priming-induced reinstatement of conditioned place preference. The anatomical structure and functional innervation of the eLPB(ChAT)–CeA(GABA) pathway were investigated by various methods such as fluorescent micro-optical sectioning tomography, virus-based neural tracing, fibre photometry, patch-clamp and designer receptor exclusively activated by a designer drug. The role of the eLPB(ChAT)–CeA(GABA) pathway in methamphetamine relapse was assessed using methamphetamine priming-induced reinstatement of conditioned place preference behaviours in male mice. We found that the eLPB(ChAT) neurons mainly projected to the central nucleus of the amygdala. A chemogenetic activation of the eLPB(ChAT) neurons in vitro or in vivo triggered the excitabilities of the CeA(GABA) neurons, which is at least in part mediated via the cholinergic receptor system. Most importantly, the chemogenetic activation of either the eLPB(ChAT) neurons or the eLPB(ChAT) neurons that project onto the central nucleus of the amygdala decreased the methamphetamine priming-induced reinstatement of conditioned place preference in mice. Our findings revealed a previously undiscovered cholinergic pathway of the eLPB(ChAT)–CeA(GABA) and showed that the activation of this pathway decreased the methamphetamine priming-induced reinstatement of conditioned place preference. Oxford University Press 2022-08-30 /pmc/articles/PMC9536296/ /pubmed/36213311 http://dx.doi.org/10.1093/braincomms/fcac219 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
He, Teng
Chen, Wenwen
Fan, Yu
Xu, Xing
Guo, Hao
Li, Nanqin
Lu, Xue
Ge, Feifei
Guan, Xiaowei
A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title_full A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title_fullStr A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title_full_unstemmed A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title_short A novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
title_sort novel cholinergic projection from the lateral parabrachial nucleus and its role in methamphetamine-primed conditioned place preference
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536296/
https://www.ncbi.nlm.nih.gov/pubmed/36213311
http://dx.doi.org/10.1093/braincomms/fcac219
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