Opposing mechanisms mediate morphine-and cocaine-induced generation of silent synapses
Published in Nature Neuroscience, 2016
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.
Recommended citation: Graziane, NM, Sun, S#, Wright, WJ#, Jang, D, Zheng, L, Huang, YH, Nestler, EJ, Wang, YT, Schlüter, OM, & Dong Y. (2016). "Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses." Nature Neuroscience. 19(17).
Paper URL | Paper PDF