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

Nicholas M. Graziane, Shichao Sun, William J. Wright, Daniel Jang, Zheng Liu, Yanhua H. Huang, Eric J. Nestler, Yu Tian Wang, Oliver M. Schlüter, Yan Dong

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


Exposures to cocaine and morphine produce similar adaptations in nucleus accumbens (NAc)-based behaviors, yet produce very different adaptations at NAc excitatory synapses. In an effort to explain this paradox, we found that both drugs induced NMDA receptor-containing, AMPA receptor-silent excitatory synapses, albeit in distinct cell types through opposing cellular mechanisms. Cocaine selectively induced silent synapses in D1-type neurons, likely via a synaptogenesis process, whereas morphine induced silent synapses in D2-type neurons via internalization of AMPA receptors from pre-existing synapses. After drug withdrawal, cocaine-generated silent synapses became 'unsilenced' by recruiting AMPA receptors to strengthen excitatory inputs to D1-type neurons, whereas morphine-generated silent synapses were likely eliminated to weaken excitatory inputs to D2-type neurons. Thus, these cell type-specific, opposing mechanisms produced 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.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalNature Neuroscience
Issue number7
StatePublished - Jul 1 2016

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


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