Previous　studies　suggest　that　the　nucleus　accumbens　shell　(AcbSh)　and　core　(AcbC)　regions　may　have　distinct　roles　in　ethanol　consumption.　N-Methyl-D-aspartate　receptor　1　(NMDAR1),　Ca2+/calmodulindependent　protein　kinase　II　(CaMKII)　and　extracellular　signal-regulated　kinases　(ERKs)　have　been　demonstrated　to　contribute　to　and　possibly　interact　in　the　molecular　mechanism　underlying　ethanol　dependence　and　relapse.　However,　little　is　known　regarding　the　mechanisms　underlying　the　effects　of　ethanol　exposure,　withdrawal,　and　re-exposure,　particularly　with　regard　to　NMDAR1-CaMKII-ERK　signaling　in　accumbens　subregions.　In　the　present　study,　rats　were　provided　with　a　6%　ethanol　solution　as　their　only　drinking　source.　We　found　that　ethanol　exerted　locomotor　stimulant　and　anxiolytic　effects　in　open　field　behaviors.　Phosphorylation　of　NMDAR1,　CaMKII　and　ERIC　was　significantly　decreased　in　the　AcbSh　and　AcbC　following　chronic　ethanol　exposure.　Ethanol　withdrawal　increased　phospho-NMDAR1　and　phospho-CaMKII　expression　in　the　AcbSh.　Ethanol　withdrawal　also　induced　an　increase　of　phosphoERK1/2　in　both　the　AcbSh　and　AcbC,　while　ethanol　re-exposure　decreased　phospho-ERK　in　the　AcbSh.　These　results　indicated　that　the　activation　of　NMDAR1-CaMKII-ERK　signaling　in　the　AcbSh　but　not　the　AcbC　would　contribute　more　to　ethanol　drinking　and　chronic　ethanol-related　negative　emotional　states.　(C)　2015　Elsevier　Ireland　Ltd.　All　rights　reserved.