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

Nat Neurosci. 2016 Jul;19(7):915-25. doi: 10.1038/nn.4313. Epub 2016 May 30.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Excitatory Postsynaptic Potentials / drug effects*
  • Male
  • Morphine / pharmacology*
  • Neuronal Plasticity / drug effects*
  • Nucleus Accumbens / drug effects
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Synapses / drug effects*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Morphine
  • Cocaine