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Studies on animal models of drug addiction indicate that persistent long-term potentiation (LTP) of excitatory synaptic transmission onto ventral tegmental area (VTA) dopamine (DA) neurons is a critical component of sustained drug seeking. However, little is known about the mechanism regulating such long-lasting changes in synaptic strength. Previously, we identified that translational control by eIF2\u03b1 phosphorylation (p-eIF2\u03b1) regulates cocaine-induced LTP in the VTA (Huang et al., 2016). Here we report that in mice with reduced p-eIF2\u03b1-mediated translation, cocaine induces persistent LTP in VTA DA neurons. Moreover, selectively inhibiting eIF2\u03b1-mediated translational control with a small molecule ISRIB, or knocking down oligophrenin-1\u2014an mRNA whose translation is controlled by p-eIF2\u03b1\u2014in the VTA also prolongs cocaine-induced LTP. This persistent LTP is mediated by the insertion of GluR2-lacking AMPARs. Collectively, our findings suggest that eIF2\u03b1-mediated translational control regulates the progression from transient to persistent cocaine-induced LTP.<\/jats:p>","DOI":"10.7554\/elife.17517","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T07:00:26Z","timestamp":1481612426000},"source":"Crossref","is-referenced-by-count":36,"title":["eIF2\u03b1-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons"],"prefix":"10.7554","volume":"5","author":[{"given":"Andon N","family":"Placzek","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, United States"},{"name":"Memory and Brain Research Center, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo Viana Di","family":"Prisco","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Baylor College of 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