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Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving
In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after drug withdrawal. This ‘incubation of cocaine craving’ is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens. However, the circuit-level adaptations mediat...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815713/ https://www.ncbi.nlm.nih.gov/pubmed/24077564 http://dx.doi.org/10.1038/nn.3533 |
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author | Lee, Brian R. Ma, Yao-ying Huang, Yanhua H. Wang, Xiusong Otaka, Mami Ishikawa, Masago Neumann, Peter A. Graziane, Nicolas M. Brown, Travis E. Suska, Anna Guo, Changyong Lobo, Mary Kay Sesack, Susan R. Wolf, Marina E. Nestler, Eric J. Shaham, Yavin Schlüter, Oliver M. Dong, Yan |
author_facet | Lee, Brian R. Ma, Yao-ying Huang, Yanhua H. Wang, Xiusong Otaka, Mami Ishikawa, Masago Neumann, Peter A. Graziane, Nicolas M. Brown, Travis E. Suska, Anna Guo, Changyong Lobo, Mary Kay Sesack, Susan R. Wolf, Marina E. Nestler, Eric J. Shaham, Yavin Schlüter, Oliver M. Dong, Yan |
author_sort | Lee, Brian R. |
collection | PubMed |
description | In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after drug withdrawal. This ‘incubation of cocaine craving’ is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens. However, the circuit-level adaptations mediating this plasticity remain elusive. Here we studied silent synapses—often regarded as immature synapses that express stable NMDA receptors with AMPA receptors either absent or labile—in basolateral amygdala-to-accumbens projection in incubation of cocaine craving. Silent synapses were detected within this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became ‘unsilenced’, a process involving synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased cocaine incubation. Our finding indicates that silent synapse-based reorganization of the amygdala-to-accumbens projection is critical for persistent cocaine craving and relapse after withdrawal. |
format | Online Article Text |
id | pubmed-3815713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-38157132014-05-01 Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving Lee, Brian R. Ma, Yao-ying Huang, Yanhua H. Wang, Xiusong Otaka, Mami Ishikawa, Masago Neumann, Peter A. Graziane, Nicolas M. Brown, Travis E. Suska, Anna Guo, Changyong Lobo, Mary Kay Sesack, Susan R. Wolf, Marina E. Nestler, Eric J. Shaham, Yavin Schlüter, Oliver M. Dong, Yan Nat Neurosci Article In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after drug withdrawal. This ‘incubation of cocaine craving’ is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens. However, the circuit-level adaptations mediating this plasticity remain elusive. Here we studied silent synapses—often regarded as immature synapses that express stable NMDA receptors with AMPA receptors either absent or labile—in basolateral amygdala-to-accumbens projection in incubation of cocaine craving. Silent synapses were detected within this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became ‘unsilenced’, a process involving synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased cocaine incubation. Our finding indicates that silent synapse-based reorganization of the amygdala-to-accumbens projection is critical for persistent cocaine craving and relapse after withdrawal. 2013-09-29 2013-11 /pmc/articles/PMC3815713/ /pubmed/24077564 http://dx.doi.org/10.1038/nn.3533 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lee, Brian R. Ma, Yao-ying Huang, Yanhua H. Wang, Xiusong Otaka, Mami Ishikawa, Masago Neumann, Peter A. Graziane, Nicolas M. Brown, Travis E. Suska, Anna Guo, Changyong Lobo, Mary Kay Sesack, Susan R. Wolf, Marina E. Nestler, Eric J. Shaham, Yavin Schlüter, Oliver M. Dong, Yan Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title | Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title_full | Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title_fullStr | Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title_full_unstemmed | Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title_short | Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
title_sort | maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815713/ https://www.ncbi.nlm.nih.gov/pubmed/24077564 http://dx.doi.org/10.1038/nn.3533 |
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