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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2015
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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. |
format | Online Article Text |
id | pubmed-4340131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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