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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07

AUTHORS

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

ABSTRACT

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. More... »

PAGES

915-925

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nn.4313

    DOI

    http://dx.doi.org/10.1038/nn.4313

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031973520

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27239940


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