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Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in meth...

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Autores principales: Chen, Han-Ting, Chen, Jin-Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340131/
https://www.ncbi.nlm.nih.gov/pubmed/25691515
http://dx.doi.org/10.1101/lm.037721.114
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author Chen, Han-Ting
Chen, Jin-Chung
author_facet Chen, Han-Ting
Chen, Jin-Chung
author_sort Chen, Han-Ting
collection PubMed
description The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning.
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spelling pubmed-43401312016-03-01 Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity Chen, Han-Ting Chen, Jin-Chung Learn Mem Research The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning. Cold Spring Harbor Laboratory Press 2015-03 /pmc/articles/PMC4340131/ /pubmed/25691515 http://dx.doi.org/10.1101/lm.037721.114 Text en © 2015 Chen and Chen; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Chen, Han-Ting
Chen, Jin-Chung
Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title_full Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title_fullStr Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title_full_unstemmed Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title_short Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity
title_sort role of the ventral tegmental area in methamphetamine extinction: ampa receptor-mediated neuroplasticity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340131/
https://www.ncbi.nlm.nih.gov/pubmed/25691515
http://dx.doi.org/10.1101/lm.037721.114
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