Sensitivity of NMDA Receptors to Acute and in Utero Ethanol Exposure

  • Steven W. Leslie
  • Melanie S. Weaver


Electrophysiological and biochemical studies have shown that N-methyl-d-aspartate (NMDA) receptors are highly sensitive to inhibition by ethanol. However, some laboratories report that very low ethanol concentrations, in the range of 5 mM or less, inhibit NMDA receptor function, while others report that the confines of ethanol sensitivity may start at somewhat higher concentrations. The review that follows addresses the question of where the literature now stands on the issue of the sensitivity of the NMDA receptor to ethanol.


NMDA Receptor Cerebellar Granule Cell Ethanol Exposure Glycine Site NMDA Receptor Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bode-Greuel, K.M. and Singer, W., 1989, The development of N-methyl-d-aspartate receptors in cat visual cortex, Brain Res. 46: 197.CrossRefGoogle Scholar
  2. Brenneman, D.E., Forsythe, I.D., Nicol, T., and Nelson, P.G., N-Methyl-d-aspartate receptors influence neuronal survival in developing spinal cord cultures, Develop. Brain Res. 51: 63.Google Scholar
  3. Brown, L.M., Leslie, S.W., Gonzales, R.A., 1991, The effects of chronic ethanol exposure on N-methyl-d-aspartate-stimulated overflow of [3H]catecholamines from rat brain, Brain Res. 547: 289.PubMedCrossRefGoogle Scholar
  4. Collingridge, G.L. and Bliss, T.V.P., 1987, NMDA receptors - their role in long-term potentiation, TINS, 10: 288.Google Scholar
  5. Cotman, C.W. and Iversen, L.L., 1987, Excitatory amino acids in the brain - focus on NMDA receptors, TINS 10: 263.Google Scholar
  6. Cotman, C.W., Monaghan, D.T., Ottersen, O.P., and Storm-Mathison, J., 1987, Anatomical organization of excitatory amino acid receptors and their pathways, TINS 10: 273.Google Scholar
  7. Dildy, J.E. and Leslie, S.W., 1989, Ethanol inhibits NMDA-induced increases in free intracellular Ca2+ in dissociated brain cells, Brain Res. 499: 383.PubMedCrossRefGoogle Scholar
  8. Dildy-Mayfield, J.E. and Leslie, S.W., 1991, Mechanism of inhibition of N-methyl-d-aspartate-stimulated increases in free intracellular Ca2+ concentration by ethanol, J. Neurochem. 56: 1536.PubMedCrossRefGoogle Scholar
  9. Dildy-Mayfield, J.E., Machu, T. and Leslie, S.W., 1991, Ethanol and voltage- or receptor-mediated increases in cytosolic Ca2+ in brain cells, Alcohol 9: 63CrossRefGoogle Scholar
  10. Farr, K.L., Montano, C.Y., Paxton, L.L., and Savage, D.D., 1988, Prenatal ethanol exposure decreases hippocampal 3H-glutamate binding in 45-day-old rats, Alcohol 5: 125.PubMedCrossRefGoogle Scholar
  11. Fink, K. and Gothert, M., 1990, Inhibition of N-methyl-d-aspartate-induced noradrenaline release by alcohols is related to their hydrophobicity, Eur. J. Pharmacol. 191: 225.PubMedCrossRefGoogle Scholar
  12. Gonzales, R.A. and Woodward, J.J., 1990, Ethanol inhibits N-methyl-d-aspartate-stimulated [3H]norepinephrine release from rat cortical slices, J. Pharmacol Exp. Ther. 253: 1138.PubMedGoogle Scholar
  13. Gonzales, R.A. and Roper, L.C., 1992, Ethanol effects on NMDA-stimulated levels of extracellular neurotransmitters by in vivo microdialysis, Alcohol & Alcoholism 27 (suppl 1): 21.Google Scholar
  14. Goodlett, C.R., Kelly, S.J., and West, J.R., 1987, Early postnatal alcohol exposure that produces high blood alcohol levels impairs development of spatial navigation learning, Psychobiol. 15: 64.Google Scholar
  15. Hoffman, P.L., Rabe, C.S., Moses, F., and Tabakoff, B., 1989, N-Methyl-d-aspartate receptors and ethanol: Inhibition of calcium flux and cyclic GMP production, J. Neurochem. 52: 1937.PubMedCrossRefGoogle Scholar
  16. Kalb, R.G. and Hockfield, S., 1990, Induction of a Neuronal Proteoglycan by the NMDA receptor in the developing spinal cord, Science 250: 294.PubMedCrossRefGoogle Scholar
  17. Kleckner, N.W. and Dingledine, R., 1991, Regulation of hippocampal NMDA receptors by magnesium and glycine during development, Mol. Brain Res. 11: 151.PubMedGoogle Scholar
  18. Kleinschmidt, A., Bear, M.F. and Singer, W., 1987, Blockade of ‘NMDA’ receptors disrupts experience-dependent plasticity of kitten striate cortex, Science 238: 355.PubMedCrossRefGoogle Scholar
  19. Leslie, S.W., Weaver, M.S., Morris, J.L., Lee, Y-.H. and Randall, P.K., 1992, Glutathione stimulation of NMPA receptor function: Effects of acute and chronic ethanol exposure, Alcohol and Alcoholism 27: 59.Google Scholar
  20. Lima-Landman, M.T.R. and Albuquerque, E.X., 1989, Ethanol potentiates and blocks NMDA-activated single-channel currents in rat hippocampal pyramidal cells, FEBS Letters 247: 61.PubMedCrossRefGoogle Scholar
  21. Lodge, D. and Johnson, K.M., 1991, Noncompetitive excitatory amino acid receptor antagonists, TIPS Special Report p. 13.Google Scholar
  22. Lovinger, D.M., White, G., and Weight, F.F., 1989, Ethanol inhibits NMDA-activated ion current in hippocampal neurons, Science 243: 1989.CrossRefGoogle Scholar
  23. Lovinger, D.M., White, G., and Weight, F.F., 1990, Ethanol inhibition of neuronal glutamate receptor function, Ann Med. 22: 247.PubMedCrossRefGoogle Scholar
  24. Lovinger, D.M., White, G., and Weight, F.F., 1990a, NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat, J. Neurosci. 10: 1372.PubMedGoogle Scholar
  25. Martin, D., Morrisett, R.A., Bian, X-P., Wilson, W.A., and Swartzwelder, H.S., 1991, Ethanol inhibition of NMD A mediated depolarizations is increased in the presence of Mg2+, Brain Res. 546: 227.PubMedCrossRefGoogle Scholar
  26. Mattson, M.P., Dou, P., and Kater. S.B., 1988, Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons, J. Neurosci. 8: 2087.PubMedGoogle Scholar
  27. Mattson, M.P., Lee, R.E., Adams, M.E., Guthrie, P.B., and Kater, S.B., 1988a, Interactions between entorhinal axons and target hippocampal neurons: A role for glutamate in the development of hippocampal circuitry, Neuron 1: 865.PubMedCrossRefGoogle Scholar
  28. Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., and Seeburg, P.H., 1992, Heteromeric NMDA receptors: Molecular and functional distinctions of subtypes, Science 256: 1217.PubMedCrossRefGoogle Scholar
  29. Morrisett, R.A., Martin, D., Wilson, W.A., Savage, D.D., and Swartzwelder, S., 1989, Prenatal exposure to ethanol decreases the sensitivity of the adult rat hippocampus to N-methyl-d-aspartate, Alcohol 6: 415.PubMedCrossRefGoogle Scholar
  30. Morrisett, R.A., Mott, D.D., Lewis, D.V., Wilson, W.A., and Swartzwelder, H.S., 1990, Reduced sensitivity of the N-methyl-d-aspartate component of synaptic transmission to magnesium in hippocampal slices from immature rats, Devel. Brain Res. 56: 257.CrossRefGoogle Scholar
  31. Oppenheim, R.W., 1991, Cell death during development of the nervous system, Annu. Rev. Neurosci. 14: 453.PubMedCrossRefGoogle Scholar
  32. Pierce, D.R. and West, J.R., 1987, Differential deficits in regional brain growth induced by postnatal alcohol, Neurotoxicol. Terotol. 9: 129.CrossRefGoogle Scholar
  33. Peoples, R.W. and Weight, F.F., 1992, Ethanol inhibition of N-methyl-d-aspartate ion current in rat hippocampal neurons is not competitive with glycine, Brain Res. 571: 342.PubMedCrossRefGoogle Scholar
  34. Rabe, C.S. and Tabakoff, B., 1990, Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-d-adpartate receptor, Mol. Pharmacol. 38: 753.PubMedGoogle Scholar
  35. Rauschecker, J.P. and Hahn, S., 1987, Ketamine-xylazine anaesthesia blocks consolidation of ocular dominance changes in kitten visual cortex, Nature 326: 183.PubMedCrossRefGoogle Scholar
  36. Savage, D.D., Queen, S.A., Sanchez, C.F., Paxton, L.L., Mahoney, J.C., Goodlett, C.R., and West, J.R., 1991a, Prenatal ethanol exposure during the last third of gestation in rat reduces hippocampal NMDA agonist binding site density in 45-day-old offspring, Alcohol 9: 37.CrossRefGoogle Scholar
  37. Savage, D.D., Montano, C.Y., Otero, M.A., and Paxton, L.L., 1991, Prenatal ethanol exposure decreases hippocampal NMDA-sensitive [3H]-glutamate binding site density in 45-day-old rats, Alcohol 8: 193.PubMedCrossRefGoogle Scholar
  38. Simon, P.E., Criswell, H.E., Johnson, K.B., Hicks, R.E., and Breese, G.B., 1991, Ethanol inhibits NMDA-evoked electrophysiological activity in vivo, J. Pharmacol. Exp. Ther. 257: 225.Google Scholar
  39. Sinclair, J.G. and Lo, G.F., 1986, Ethanol blocks tetanic and calcium-induced long-term potentiation in the hippocampal slice, Gen. Pharmacol. 17: 231.PubMedCrossRefGoogle Scholar
  40. Siviy, S.M., Buchwald, N.A., and Levine, M.S., 1991, Enhanced responses to NMDA receptor activation in the developing cat caudate nucleus, Neurosci. Letters 132: 77.CrossRefGoogle Scholar
  41. Sugihara, H., Moriyoshi, K., Ishii, T., Masu, M., and Nakanishi, S., 1992, Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing, Biochem. Biophys. Res. Comm. 185: 826.PubMedCrossRefGoogle Scholar
  42. Teichberg, V.I., Tal, N., Goldberg, O., and Luini, A., 1984, Barbiturates, alcohols and the CNS excitatory neurotransmission: Specific effects on the kainate and quisqualate receptors, Brain Res. 291: 285.PubMedCrossRefGoogle Scholar
  43. White, G., Lovinger, D.M., and Weight, F.F., 1990, Ethanol inhibits NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron, Brain Res. 507: 332.PubMedCrossRefGoogle Scholar
  44. Woodward, J.J. and Gonzales, R.A., 1990, Ethanol inhibition of N-methyl-d-aspartate-stimulated endogenous dopamine release from rat striatal slices: Reversal by glycine, J. Neurochem. 54: 712.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Steven W. Leslie
    • 1
    • 2
  • Melanie S. Weaver
    • 2
  1. 1.Division of PharmacologyCollege of PharmacologyAustinUSA
  2. 2.Institute for NeuroscienceThe University of Texas at AustinAustinUSA

Personalised recommendations