title: Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses.
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.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Graziane
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Shichao
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Wright
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jang
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.affiliation: Brain Research Centre and Department of Medicine, Vancouver Coastal Health Research Institute, University of British Columbia Vancouver, British Columbia, Canada.
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; D003042:Cocaine