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Title: Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons. Author: Maler JM, Esselmann H, Wiltfang J, Kunz N, Lewczuk P, Reulbach U, Bleich S, Rüther E, Kornhuber J. Journal: Brain Res; 2005 Aug 09; 1052(2):156-62. PubMed ID: 16009352. Abstract: The present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR2B were quantified by Western immunoblot analysis. Exposure to ethanol (50 mM) caused an increase in the levels of NR1 (137 +/- 11% of untreated control, P = 0.009), NR2A (128 +/- 14%, P = 0.022) and NR2B (136 +/- 19%, P = 0.012). Coincubation with memantine (10 microM) completely blocked the ethanol-induced up-regulation of NR1 (102 +/- 4%), NR2A (95 +/- 7%) and NR2B (105 +/- 13%). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6%, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence.[Abstract] [Full Text] [Related] [New Search]