PMID- 20603193 OWN - NLM STAT- MEDLINE DCOM- 20110120 LR - 20220311 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 170 IP - 2 DP - 2010 Oct 13 TI - N-methyl-D-aspartate receptor subunit expression in adult and adolescent brain following chronic ethanol exposure. PG - 645-54 LID - 10.1016/j.neuroscience.2010.06.065 [doi] AB - Substantial evidence suggests that glutamatergic neurotransmission is a critical mediator of the experience-dependent synaptic plasticity that may underlie alcohol dependence. Substance abuse typically begins in adolescence; therefore, the impact of alcohol on glutamatergic systems during this critical time in brain development is of particular importance. The N-methyl-d-aspartate receptor (NMDAR) is involved in developmental mechanisms underlying neuronal differentiation and synaptogenesis and as such may be a target system for alcohol effects during adolescence. In the present study quantitative biochemical determinations were made of the relative abundance of different protein expressions of NMDAR subunits in adolescents and adults after 2 weeks of ethanol vapor exposure, and 24 h and 2 weeks following withdrawal. After 2 weeks of ethanol vapor exposure N-methyl-d-aspartate receptor NR1 subunit (NR1), N-methyl-d-aspartate receptor NR2A subunit (NR2A), and N-methyl-d-aspartate receptor NR2B subunit (NR2B) subunit expression was found to be increased in hippocampus of the adults. In contrast, 2 weeks of ethanol exposure resulted in no significant changes in NR1 and NR2B subunits and a reduction NR2A subunit expression in hippocampus in adolescents. Twenty-four h and 2 weeks following withdrawal from ethanol vapor NR1 and NR2A subunit expression in hippocampus was decreased in adolescents, whereas in adults it had returned to control levels. In frontal cortex, 2 weeks of chronic ethanol exposure produced decreases in NR1 subunit expression in both adults and adolescents but also produced decreases in NR2A and NR2B subunit expression in adults that returned or exceeded control levels by 2 weeks following withdrawal from ethanol vapor. These results demonstrate that NMDAR subunit composition can be modulated differentially between adolescents and adults by chronic ethanol exposure and withdrawal. These developmental differences in NMDAR subunits composition may also be associated with the enhanced vulnerability of the adolescent brain to ethanol dependence. CI - Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Pian, J P AU - Pian JP AD - Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. FAU - Criado, J R AU - Criado JR FAU - Milner, R AU - Milner R FAU - Ehlers, C L AU - Ehlers CL LA - eng GR - R01 AA014339/AA/NIAAA NIH HHS/United States GR - AA014339/AA/NIAAA NIH HHS/United States GR - R01 AA006059/AA/NIAAA NIH HHS/United States GR - T32 AA007456/AA/NIAAA NIH HHS/United States GR - AA006059/AA/NIAAA NIH HHS/United States GR - 5T32 AA007456/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100717 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Protein Isoforms) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 3K9958V90M (Ethanol) SB - IM MH - Administration, Inhalation MH - Age Factors MH - Animals MH - Body Weight/drug effects MH - Ethanol/administration & dosage/blood/*pharmacology MH - Frontal Lobe/*drug effects/metabolism MH - Gene Expression Regulation, Developmental/*drug effects MH - Hippocampus/*drug effects/metabolism MH - Male MH - Protein Isoforms/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Substance Withdrawal Syndrome/*metabolism MH - Time Factors PMC - PMC2945397 MID - NIHMS228406 EDAT- 2010/07/07 06:00 MHDA- 2011/01/21 06:00 PMCR- 2011/10/13 CRDT- 2010/07/07 06:00 PHST- 2010/02/04 00:00 [received] PHST- 2010/06/16 00:00 [revised] PHST- 2010/06/25 00:00 [accepted] PHST- 2010/07/07 06:00 [entrez] PHST- 2010/07/07 06:00 [pubmed] PHST- 2011/01/21 06:00 [medline] PHST- 2011/10/13 00:00 [pmc-release] AID - S0306-4522(10)00937-1 [pii] AID - 10.1016/j.neuroscience.2010.06.065 [doi] PST - ppublish SO - Neuroscience. 2010 Oct 13;170(2):645-54. doi: 10.1016/j.neuroscience.2010.06.065. Epub 2010 Jul 17.