Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behavior...

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Autores principales: Liu, Min, Tan, Xu, Liu, E, Hang, Zhaofang, Song, Ruiheng, Mu, Shouhong, Han, Weikai, Yue, Qingwei, Sun, Jinhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266452/
https://www.ncbi.nlm.nih.gov/pubmed/35806315
http://dx.doi.org/10.3390/ijms23137305
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author Liu, Min
Tan, Xu
Liu, E
Hang, Zhaofang
Song, Ruiheng
Mu, Shouhong
Han, Weikai
Yue, Qingwei
Sun, Jinhao
author_facet Liu, Min
Tan, Xu
Liu, E
Hang, Zhaofang
Song, Ruiheng
Mu, Shouhong
Han, Weikai
Yue, Qingwei
Sun, Jinhao
author_sort Liu, Min
collection PubMed
description Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.
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spelling pubmed-92664522022-07-09 Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression Liu, Min Tan, Xu Liu, E Hang, Zhaofang Song, Ruiheng Mu, Shouhong Han, Weikai Yue, Qingwei Sun, Jinhao Int J Mol Sci Article Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease. MDPI 2022-06-30 /pmc/articles/PMC9266452/ /pubmed/35806315 http://dx.doi.org/10.3390/ijms23137305 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Min
Tan, Xu
Liu, E
Hang, Zhaofang
Song, Ruiheng
Mu, Shouhong
Han, Weikai
Yue, Qingwei
Sun, Jinhao
Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title_full Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title_fullStr Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title_full_unstemmed Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title_short Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression
title_sort inactivation of the lateral hypothalamus attenuates methamphetamine-induced conditioned place preference through regulation of kcnq3 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266452/
https://www.ncbi.nlm.nih.gov/pubmed/35806315
http://dx.doi.org/10.3390/ijms23137305
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