title: Differential phosphorylation of NMDAR1-CaMKII-MAPKs in the rat nucleus accumbens following chronic ethanol exposure.
abstract: 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), Ca(2+)/calmodulin-dependent 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 ERK 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 phospho-ERK1/2 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.
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China; Department of Forensic Medicine, Xinxiang Medicine University, Xinxiang 453003, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China.
authors.forename: YunPeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, PR China. Electronic address: laijh1011@hotmail.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lai
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004644:Emotions / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Ca(2+)/calmodulin-dependent protein kinase II; Ethanol; Extracellular signal-regulated kinases; N-Methyl-d-aspartate receptors; Nucleus accumbens