4.7 Article

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

Journal

NATURE NEUROSCIENCE
Volume 19, Issue 7, Pages 915-925

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4313

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Funding

  1. NIH NIDA [DA035805, MH101147, DA008227, DA014133, DA023206, DA034856, DA040620]
  2. Pennsylvania Department of Health

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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.

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