Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons.

Juan Manuel Maler, Hermann Esselmann, Jens Wiltfang, Nikolaus Kunz, Piotr Lewczuk, Udo Reulbach, Stefan Bleich, Eckart Rüther, Johannes Kornhuber

Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Germany. Manuel.Maler@psych.imed.uni-erlangen.de

Brain research 2005 Aug 9

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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.

Citation

Juan Manuel Maler, Hermann Esselmann, Jens Wiltfang, Nikolaus Kunz, Piotr Lewczuk, Udo Reulbach, Stefan Bleich, Eckart Rüther, Johannes Kornhuber. Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons. Brain research. 2005 Aug 9;1052(2):156-62