Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses

Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. Here, we explain this paradox by showing that both drugs induce NMDA receptor-containing, AMPA receptor (AMPAR)-silent excitato...

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Main Authors:	Graziane, Nicholas M., Sun, Shichao, Wright, William J., Jang, Daniel, Liu, Zheng, Huang, Yanhua H., Nestler, Eric J., Wang, Yu Tian, Schlüter, Oliver M., Dong, Yan
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925174/

id	pubmed-4925174
recordtype	oai_dc
spelling	pubmed-49251742016-11-30 Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses Graziane, Nicholas M. Sun, Shichao Wright, William J. Jang, Daniel Liu, Zheng Huang, Yanhua H. Nestler, Eric J. Wang, Yu Tian Schlüter, Oliver M. Dong, Yan Article Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. Here, we explain this paradox by showing that both drugs induce NMDA receptor-containing, AMPA receptor (AMPAR)-silent excitatory synapses, but in distinct cell types through opposing cellular mechanisms: cocaine selectively induces silent synapses in D1-type neurons likely via a synaptogenesis process, whereas morphine induces silent synapses in D2-type neurons via internalization of AMPARs from pre-existing synapses. After drug withdrawal, cocaine-generated silent synapses become ‘unsilenced’ by recruiting AMPARs to strengthen excitatory inputs to D1-type neurons, while morphine-generated silent synapses are likely eliminated to weaken excitatory inputs to D2-type neurons. Thus, these cell-type specific, opposing mechanisms produce the same net shift of the balance between excitatory inputs to D1- and D2-type NAc neurons, which may underlie certain common alterations in NAc-based behaviors induced by both classes of drugs. 2016-05-30 2016-07 /pmc/articles/PMC4925174/ /pubmed/27239940 http://dx.doi.org/10.1038/nn.4313 Text en Users may view, print, copy, and download 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
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Graziane, Nicholas M. Sun, Shichao Wright, William J. Jang, Daniel Liu, Zheng Huang, Yanhua H. Nestler, Eric J. Wang, Yu Tian Schlüter, Oliver M. Dong, Yan
spellingShingle	Graziane, Nicholas M. Sun, Shichao Wright, William J. Jang, Daniel Liu, Zheng Huang, Yanhua H. Nestler, Eric J. Wang, Yu Tian Schlüter, Oliver M. Dong, Yan Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
author_facet	Graziane, Nicholas M. Sun, Shichao Wright, William J. Jang, Daniel Liu, Zheng Huang, Yanhua H. Nestler, Eric J. Wang, Yu Tian Schlüter, Oliver M. Dong, Yan
author_sort	Graziane, Nicholas M.
title	Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
title_short	Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
title_full	Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
title_fullStr	Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
title_full_unstemmed	Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
title_sort	opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses
description	Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. Here, we explain this paradox by showing that both drugs induce NMDA receptor-containing, AMPA receptor (AMPAR)-silent excitatory synapses, but in distinct cell types through opposing cellular mechanisms: cocaine selectively induces silent synapses in D1-type neurons likely via a synaptogenesis process, whereas morphine induces silent synapses in D2-type neurons via internalization of AMPARs from pre-existing synapses. After drug withdrawal, cocaine-generated silent synapses become ‘unsilenced’ by recruiting AMPARs to strengthen excitatory inputs to D1-type neurons, while morphine-generated silent synapses are likely eliminated to weaken excitatory inputs to D2-type neurons. Thus, these cell-type specific, opposing mechanisms produce the same net shift of the balance between excitatory inputs to D1- and D2-type NAc neurons, which may underlie certain common alterations in NAc-based behaviors induced by both classes of drugs.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925174/
_version_	1613601031706378240

Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses

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