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Neurochemical Research

, Volume 44, Issue 1, pp 78–88 | Cite as

GluN2B Subunit of the NMDA Receptor: The Keystone of the Effects of Alcohol During Neurodevelopment

  • Mickaël Naassila
  • Olivier PierreficheEmail author
Original Paper

Abstract

The glutamatergic system plays a central role in both the acute and chronic effects of ethanol. Among all the glutamate receptors the ionotropic NMDA receptors are crucial because of their role in synaptic plasticity. A large body of evidences suggests that short-term and long-term effects of ethanol may change synaptic plasticity via an alteration of the expression of the GluN2B subunit, one constitutive element of the NMDA receptor. The present review is focusing on the role of the GluN2B subunit after ethanol exposure during early life (in utero and adolescence) and also at adulthood. The roles of other NMDA subunits are also discussed in the context of the increasing evidence that the ratio of the different subunits, such as GluN2A-to-GluN2B, seems to better reflect the effects of ethanol and to explain how ethanol exposure can have short lasting and long lasting effects on synaptic plasticity, cognitive processes and some of the ethanol-related behaviors.

Keywords

GLUN2 subunit NMDA Alcohol Glutamate In utero Adolescence 

References

  1. 1.
    Roth S, Seeman P (1972) Meyer-Overton rule of anesthesia; negative narcotics do not. Biochim Biophys Acta 255:207–219Google Scholar
  2. 2.
    Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243(4899):1721–1724Google Scholar
  3. 3.
    Chen X, Michaelis ML, Michaelis EK (1997) Effects of chronic ethanol treatment on the expression of calcium transport carriers and NMDA/glutamate receptor proteins in brain synaptic membranes. J Neurochem 69:1559–1569Google Scholar
  4. 4.
    Michaelis EK (1997) L-glutamate and N-methyl-D-aspartate receptors: learning, growth, and death in the mammalian brain. Nutrition 13:696–697Google Scholar
  5. 5.
    Paoletti P, Bellone C, Zhou Q (2013) NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci 14:383–400Google Scholar
  6. 6.
    Lau CG, Zukin RS (2007) NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 8:413–426Google Scholar
  7. 7.
    Lüscher C (2013) Drug-evoked synaptic plasticity causing addictive behavior. J Neurosci 33:17641–17646Google Scholar
  8. 8.
    Holmes A, Spanagel R, Krystal JH (2013) Glutamatergic targets for new alcohol medications. Psychopharmacology 229:539–554Google Scholar
  9. 9.
    Hopf FW (2017) Do specific NMDA receptor subunits act as gateways for addictive behaviors? Genes Brain Behav 16(1):118–138Google Scholar
  10. 10.
    Nagy J (2004) The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence. Curr Drug Targets CNS Neurol Disord 3:169–179Google Scholar
  11. 11.
    Cavara NA, Hollmann M (2008) Shuffling the deck anew: how NR3 tweaks NMDA receptor function. Mol Neurobiol 38:16–26Google Scholar
  12. 12.
    Hoffman PL, Bhave SV, Kumar KN, Iorio KR, Snell LD, Tabakoff B, Michaelis EK (1996) The 71 kDa glutamate-binding protein is increased in cerebellar granule cells after chronic ethanol treatment. Brain Res Mol Brain Res 39:167–176Google Scholar
  13. 13.
    Gonda X (2012) Basic pharmacology of NMDA receptors. Curr Pharm Des 18:1558–1567Google Scholar
  14. 14.
    Barondes SH, Traynor ME, Schlapfer WT, Woodson PB (1979) Rapid adaptation to neuronal membrane effects of ethanol and low temperature: some speculations on mechanism. Drug Alcohol Depend 4:155–166Google Scholar
  15. 15.
    Alling C, Liljequist S, Engel J (1982) The effect of chronic ethanol administration on lipids and fatty acids in subcellular fractions of rat brain. Med Biol 60:149–154Google Scholar
  16. 16.
    Smith TL, Gerhart MJ (1982) Alterations in brain lipid composition of mice made physically dependent to ethanol. Life Sci 31:1419–1425Google Scholar
  17. 17.
    Wing DR, Harvey DJ, Hughes J, Dunbar PG, McPherson KA, Paton WD (1982) Effects of chronic ethanol administration on the composition of membrane lipids in the mouse. Biochem Pharmacol 31:3431–3439Google Scholar
  18. 18.
    Michaelis EK, Michaelis ML, Freed WJ (1980) Chronic ethanol intake and synaptosomal glutamate binding activity. Adv Exp Med Biol 126:43–56Google Scholar
  19. 19.
    Michaelis EK, Chang HH, Roy S, McFaul JA, Zimbrick JD (1983) Ethanol effects on synaptic glutamate receptor function and on membrane lipid organization. Pharmacol Biochem Behav 18(Suppl 1):1–6Google Scholar
  20. 20.
    Reddy VD, Padmavathi P, Bulle S, Hebbani AV, Marthadu SB, Venugopalacharyulu NC, Maturu P, Varadacharyulu NC (2017) Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: a protective role of vitamin E. Neurotoxicol Teratol 63:60–65Google Scholar
  21. 21.
    Le Bail M, Martineau M, Sacchi S, Yatsenko N, Radzishevsky I, Conrod S, Ait Ouares K, Wolosker H, Pollegioni L, Billard JM, Mothet JP (2015) Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus. Proc Natl Acad Sci USA 112:E204–E213Google Scholar
  22. 22.
    Freed WJ, Michaelis EK (1978) Glutamic acid and ethanol dependence. Pharmacol Biochem Behav 8:509–514Google Scholar
  23. 23.
    Michaelis EK, Zimbrick JD, McFaul JA, Lampe RA, Michaelis ML (1980) Ethanol effects on synaptic glutamate receptors and on liposomal membrane structure. Pharmacol Biochem Behav 13(Suppl 1):197–202Google Scholar
  24. 24.
    Woodward JJ (2000) Ethanol and NMDA receptor signaling. Crit Rev Neurobiol 14:69–89Google Scholar
  25. 25.
    Ronald KM, Mirshahi T, Woodward JJ (2001) Ethanol inhibition of N-methyl-D-aspartate receptors is reduced by site-directed mutagenesis of a transmembrane domain phenylalanine residue. J Biol Chem 276:44729–44735Google Scholar
  26. 26.
    Smothers CT, Woodward JJ (2006) Effects of amino acid substitutions in transmembrane domains of the NR1 subunit on the ethanol inhibition of recombinant N-methyl-D-aspartate receptors. Alcohol Clin Exp Res 30:523–530Google Scholar
  27. 27.
    Salous AK, Ren H, Lamb KA, Hu XQ, Lipsky RH, Peoples RW (2009) Differential actions of ethanol and trichloroethanol at sites in the M3 and M4 domains of the NMDA receptor GluN2A (NR2A) subunit. Br J Pharmacol 158:1395–1404Google Scholar
  28. 28.
    Xu M, Smothers CT, Trudell J, Woodward JJ (2012) Ethanol inhibition of constitutively open N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 340:218–226Google Scholar
  29. 29.
    Ren H, Zhao Y, Wu M, Peoples RW (2013) A novel alcohol-sensitive position in the N-methyl-D-aspartate receptor GluN2A subunit M3 domain regulates agonist affinity and ion channel gating. Mol Pharmacol 84:501–510Google Scholar
  30. 30.
    Honse Y, Ren H, Lipsky RH, Peoples RW (2004) Sites in the fourth membrane-associated domain regulate alcohol sensitivity of the NMDA receptor. Neuropharmacology 46:647–654Google Scholar
  31. 31.
    Ren H, Zhao Y, Wu M, Dwyer DS, Peoples RW (2017) Two adjacent phenylalanines in the NMDA receptor GluN2A subunit M3 domain interactively regulate alcohol sensitivity and ion channel gating. Neuropharmacology 114:20–33Google Scholar
  32. 32.
    Ren H, Zhao Y, Dwyer DS, Peoples RW (2012) Interactions among positions in the third and fourth membrane-associated domains at the intersubunit interface of the N-methyl-D-aspartate receptor forming sites of alcohol action. J Biol Chem 287:27302–27312Google Scholar
  33. 33.
    Ren H, Salous AK, Paul JM, Lamb KA, Dwyer DS, Peoples RW (2008) Functional interactions of alcohol-sensitive sites in the N-methyl-D-aspartate receptor M3 and M4 domains. J Biol Chem 283:8250–8257Google Scholar
  34. 34.
    Ren H, Salous AK, Paul JM, Lipsky RH, Peoples RW (2007) Mutations at F637 in the NMDA receptor NR2A subunit M3 domain influence agonist potency, ion channel gating and alcohol action. Br J Pharmacol 151:749–757Google Scholar
  35. 35.
    Smothers CT, Jin C, Woodward JJ (2013) Deletion of the N-terminal domain alters the ethanol inhibition of N-methyl-D-aspartate receptors in a subunit-dependent manner. Alcohol Clin Exp Res 37:1882–1890Google Scholar
  36. 36.
    Hughes BA, Woodward JJ (2016) Disruption of S2-M4 linker coupling reveals novel subunit-specific contributions to N-methyl-d-aspartate receptor function and ethanol sensitivity. Neuropharmacology 105:96–105Google Scholar
  37. 37.
    Zhao Y, Ren H, Dwyer DS, Peoples RW (2015) Different sites of alcohol action in the NMDA receptor GluN2A and GluN2B subunits. Neuropharmacology 97:240–250Google Scholar
  38. 38.
    Zhao Y, Ren H, Peoples RW (2016) Intersubunit interactions at putative sites of ethanol action in the M3 and M4 domains of the NMDA receptor GluN1 and GluN2B subunits. Br J Pharmacol 173:1950–1965Google Scholar
  39. 39.
    Colton CA, Colton JS (1977) Depression of glutamate-mediated synaptic transmission by benzyl alcohol. Can J Physiol Pharmacol 55:917–922Google Scholar
  40. 40.
    Gruol DL (1982) Ethanol alters synaptic activity in cultured spinal cord neurons. Brain Res 243:25–33Google Scholar
  41. 41.
    Druse MJ (1981) Effects of maternal ethanol consumption of neurotransmitters and lipids in offspring. Neurobehav Toxicol Teratol 3:81–87Google Scholar
  42. 42.
    Penn PE, McBride WJ, Lumeng L, Gaff TM, Li TK (1978) Neurochemical and operant behavioral studies of a strain of alcohol-preferring rats. Pharmacol Biochem Behav 8:475–481Google Scholar
  43. 43.
    Lovinger DM, White G, Weight FF (1990) NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. J Neurosci 10:1372–1379Google Scholar
  44. 44.
    Goodwani S, Saternos H, Alasmari F, Sari Y (2017) Metabotropic and ionotropic glutamate receptors as potential targets for the treatment of alcohol use disorder. Neurosci Biobehav Rev 77:14–31Google Scholar
  45. 45.
    Jin C, Woodward JJ (2006) Effects of 8 different NR1 splice variants on the ethanol inhibition of recombinant NMDA receptors. Alcohol Clin Exp Res 30:673–679Google Scholar
  46. 46.
    Lovinger DM (1995) Developmental decrease in ethanol inhibition of N-methyl-D-aspartate receptors in rat neocortical neurons: relation to the actions of ifenprodil. J Pharmacol Exp Ther 274:164–172Google Scholar
  47. 47.
    Wang J, Lanfranco MF, Gibb SL, Yowell QV, Carnicella S, Ron D (2010) Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse. J Neurosci 30:10187–10198Google Scholar
  48. 48.
    Wills TA, Klug JR, Silberman Y, Baucum AJ, Weitlauf C, Colbran RJ, Delpire E, Winder DG (2012) GluN2B subunit deletion reveals key role in acute and chronic ethanol sensitivity of glutamate synapses in bed nucleus of the stria terminalis. Proc Natl Acad Sci USA 109:E278–E287Google Scholar
  49. 49.
    Badanich KA, Mulholland PJ, Beckley JT, Trantham-Davidson H, Woodward JJ (2013) Ethanol reduces neuronal excitability of lateral orbitofrontal cortex neurons via a glycine receptor dependent mechanism. Neuropsychopharmacology 38:1176–1188Google Scholar
  50. 50.
    Swartzwelder HS, Wilson WA, Tayyeb MI (1995) Differential sensitivity of NMDA receptor-mediated synaptic potentials to ethanol in immature versus mature hippocampus. Alcohol Clin Exp Res 19:320–323Google Scholar
  51. 51.
    Popp RL, Lickteig RL, Lovinger DM (1999) Factors that enhance ethanol inhibition of N-methyl-D-aspartate receptors in cerebellar granule cells. J Pharmacol Exp Ther 289:1564–1574Google Scholar
  52. 52.
    Jin C, Smothers C, Woodward JJ (2008) Enhanced ethanol inhibition of recombinant NMDA receptors by magnesium: role of NR3 subunits. Alcohol Clin Exp Res 32:1059–1066Google Scholar
  53. 53.
    Yaka R, Tang KC, Camarini R, Janak PH, Ron D (3003) Fyn kinase and NR2B-containing NMDA receptors regulate acute ethanol sensitivity but not ethanol intake or conditioned reward. Alcohol Clin Exp Res 27:1736–1742Google Scholar
  54. 54.
    Michaelis EK, Chen X, Joseph DB, Hurlbert M, Kumar KN, Michaelis ML (1996) Ethanol-induced inhibition of [3H]thienylcyclohexylpiperidine (TCP) binding to NMDA receptors in brain synaptic membranes and to a purified protein complex. J Neurochem 67:201–211Google Scholar
  55. 55.
    Bao X, Hui D, Naassila M, Michaelis EK (2001) Chronic ethanol exposure increases gene transcription of subunits of an N-methyl-D-aspartate receptor-like complex in cortical neurons in culture. Neurosci Lett 315:5–8Google Scholar
  56. 56.
    Kumari M, Ticku MK (2000) Regulation of NMDA receptors by ethanol. Prog Drug Res 54:152–189Google Scholar
  57. 57.
    Nona CN, Li R, Nobrega JN (2014) Altered NMDA receptor subunit gene expression in brains of mice showing high vs. low sensitization to ethanol. Behav Brain Res 260:58–66Google Scholar
  58. 58.
    Coune F, Silvestre de Ferron B, González-Marín MC, Antol J, Naassila M, Pierrefiche O (2017) Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus. Synapse.  https://doi.org/10.1002/syn.21899 Google Scholar
  59. 59.
    Kervern M, Silvestre de Ferron B, Alaux-Cantin S, Fedorenko O, Antol J, Naassila M, Pierrefiche O (2015) Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus. Hippocampus 25:912–923Google Scholar
  60. 60.
    Carpenter-Hyland EP, Woodward JJ, Chandler LJ (2004) Chronic ethanol induces synaptic but not extrasynaptic targeting of NMDA receptors. J Neurosci 24:7859–7868Google Scholar
  61. 61.
    Qiang M, Denny AD, Ticku MK (2007) Chronic intermittent ethanol treatment selectively alters N-methyl-D-aspartate receptor subunit surface expression in cultured cortical neurons. Mol Pharmacol 72:95–102Google Scholar
  62. 62.
    Sheela Rani CS, Ticku MK (2006) Comparison of chronic ethanol and chronic intermittent ethanol treatments on the expression of GABA(A) and NMDA receptor subunits. Alcohol 38:89–97Google Scholar
  63. 63.
    McGuier NS, Padula AE, Mulholland PJ, Chandler LJ (2015) Homer2 deletion alters dendritic spine morphology but not alcohol-associated adaptations in GluN2B-containing N-methyl-D-aspartate receptors in the nucleus accumbens. Front Pharmacol 6:28Google Scholar
  64. 64.
    Renteria R, Maier EY, Buske TR, Morrisett RA (2017) Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure. Neuropharmacology 112:164–171Google Scholar
  65. 65.
    Beckley JT, Laguesse S, Phamluong K, Morisot N, Wegner SA, Ron D (2016) The first alcohol drink triggers mTORC1-dependent synaptic plasticity in nucleus accumbens dopamine D1 receptor neurons. J Neurosci 36:701–713Google Scholar
  66. 66.
    Silvestre de Ferron B, Bennouar KE, Kervern M, Alaux-Cantin S, Robert A, Rabiant K, Antol J, Naassila M, Pierrefiche O (2015) Two binges of ethanol a day keep the memory away in adolescent rats: key role for GLUN2B subunit. Int J Neuropsychopharmacol.  https://doi.org/10.1093/ijnp/pyv087 Google Scholar
  67. 67.
    Kalluri HS, Mehta AK, Ticku MK (1998) Up-regulation of NMDA receptor subunits in rat brain following chronic ethanol treatment. Brain Res Mol Brain Res 58:221–224Google Scholar
  68. 68.
    Radke AK, Jury NJ, Kocharian A, Marcinkiewcz CA, Lowery-Gionta EG, Pleil KE, McElligott ZA, McKlveen JM, Kash TL, Holmes A (2017) Chronic EtOH effects on putative measures of compulsive behavior in mice. Addict Biol 22:423–434Google Scholar
  69. 69.
    Radke AK, Nakazawa K, Holmes A (2015) Cortical GluN2B deletion attenuates punished suppression of food reward-seeking. Psychopharmacology 232:3753–3761Google Scholar
  70. 70.
    Nimitvilai S, Lopez MF, Mulholland PJ, Woodward JJ (2016) Chronic intermittent ethanol exposure enhances the excitability and synaptic plasticity of lateral orbitofrontal cortex neurons and induces a tolerance to the acute inhibitory actions of ethanol. Neuropsychopharmacology 41:1112–1127Google Scholar
  71. 71.
    Kash TL, Matthews RT, Winder DG (2008) Alcohol inhibits NR2B-containing NMDA receptors in the ventral bed nucleus of the stria terminalis. Neuropsychopharmacology 33:1379–1390Google Scholar
  72. 72.
    Hsieh WK, Lin HH, Lai CC (2009) Involvement of protein kinase C and Src tyrosine kinase in acute tolerance to ethanol inhibition of spinal NMDA-induced pressor responses in rats. Br J Pharmacol 158:806–818Google Scholar
  73. 73.
    Enoch MA, Rosser AA, Zhou Z, Mash DC, Yuan Q, Goldman D (2014) Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine. Genes Brain Behav 13:758–768Google Scholar
  74. 74.
    Krystal JH, Petrakis IL, Limoncelli D, Nappi SK, Trevisan L, Pittman B, D’Souza DC, Suckow RF (2011) Characterization of the interactive effects of glycine and D-cycloserine in men: further evidence for enhanced NMDA receptor function associated with human alcohol dependence. Neuropsychopharmacology 36:701–710Google Scholar
  75. 75.
    Iqbal U, Brien JF, Kapoor A, Matthews SG, Reynolds JN (2006) Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate release in the hippocampus of the near-term foetal guinea pig. J Neuroendocrinol 18:826–834Google Scholar
  76. 76.
    Naassila M, Daoust M (2002) Effect of prenatal and postnatal ethanol exposure on the developmental profile of mRNAs encoding NMDA receptor subunits in rat hippocampus. J Neurochem 80:850–860Google Scholar
  77. 77.
    Barbier E, Pierrefiche O, Vaudry D, Vaudry H, Daoust M, Naassila M (2008) Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure. Neuropharmacology 55:1199–1211Google Scholar
  78. 78.
    Dubois C, Houchi H, Naassila M, Daoust M, Pierrefiche O (2008) Blunted response to low oxygen of rat respiratory network after perinatal ethanol exposure: involvement of inhibitory control. J Physiol 586:1413–1427Google Scholar
  79. 79.
    Kervern M, Dubois C, Naassila M, Daoust M, Pierrefiche O (2009) Perinatal alcohol exposure in rat induces long-term depression of respiration after episodic hypoxia. Am J Respir Crit Care Med 179:608–614Google Scholar
  80. 80.
    Brolese G, Lunardi P, Broetto N, Engelke DS, Lírio F, Batassini C, Tramontina AC, Gonçalves CA (2014) Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats. Behav Brain Res 269:175–184Google Scholar
  81. 81.
    Sickmann HM, Patten AR, Morch K, Sawchuk S, Zhang C, Parton R, Szlavik L, Christie BR (2014) Prenatal ethanol exposure has sex-specific effects on hippocampal long-term potentiation. Hippocampus 24:54–64Google Scholar
  82. 82.
    Nixon K, Hughes PD, Amsel A, Leslie SW (2004) NMDA receptor subunit expression after combined prenatal and postnatal exposure to ethanol. Alcohol Clin Exp Res 28:105–112Google Scholar
  83. 83.
    Nixon K, Hughes PD, Amsel A, Leslie SW (2002) NMDA receptor subunit expression following early postnatal exposure to ethanol. Brain Res Dev Brain Res 139:295–299Google Scholar
  84. 84.
    Samudio-Ruiz SL, Allan AM, Sheema S, Caldwell KK (2010) Hippocampal N-methyl-D-aspartate receptor subunit expression profiles in a mouse model of prenatal alcohol exposure. Alcohol Clin Exp Res 34:342–353Google Scholar
  85. 85.
    Bird CW, Candelaria-Cook FT, Magcalas CM, Davies S, Valenzuela CF, Savage DD, Hamilton DA (2015) Moderate prenatal alcohol exposure enhances GluN2B containing NMDA receptor binding and ifenprodil sensitivity in rat agranular insular cortex. PLoS ONE 10(3):e0118721Google Scholar
  86. 86.
    Brady ML, Diaz MR, Iuso A, Everett JC, Valenzuela CF, Caldwell KK (2013) Moderate prenatal alcohol exposure reduces plasticity and alters NMDA receptor subunit composition in the dentate gyrus. J Neurosci 33:1062–1067Google Scholar
  87. 87.
    Zink M, Ferbert T, Frank ST, Seufert P, Gebicke-Haerter PJ, Spanagel R (2011) Perinatal exposure to alcohol disturbs spatial learning and glutamate transmission-related gene expression in the adult hippocampus. Eur J Neurosci 34:457–468Google Scholar
  88. 88.
    Hughes PD, Kim YN, Randall PK, Leslie SW (1998) Effect of prenatal ethanol exposure on the developmental profile of the NMDA receptor subunits in rat forebrain and hippocampus. Alcohol Clin Exp Res 22:1255–1261Google Scholar
  89. 89.
    Schlegel RN, Spiers JG, Moritz KM, Cullen CL, Björkman ST, Paravicini TM (2017) Maternal hypomagnesemia alters hippocampal NMDAR subunit expression and programs anxiety-like behaviour in adult offspring. Behav Brain Res 328:39–47Google Scholar
  90. 90.
    Huang Y, Shen W, Su J, Cheng B, Li D, Liu G, Zhou WX, Zhang YX (2017) Modulating the balance of synaptic and extrasynaptic NMDA receptors shows positive effects against amyloid-β-induced neurotoxicity. J Alzheimers Dis 57:885–897Google Scholar
  91. 91.
    Loddenkemper T, Talos DM, Cleary RT, Joseph A, Sánchez Fernández I, Alexopoulos A, Kotagal P, Najm I, Jensen FE (2014) Subunit composition of glutamate and gamma-aminobutyric acid receptors in status epilepticus. Epilepsy Res 108:605–615Google Scholar
  92. 92.
    Holehonnur R, Phensy AJ, Kim LJ, Milivojevic M, Vuong D, Daison DK, Alex S, Tiner M, Jones LE, Kroener S, Ploski JE (2016) Increasing the GluN2A/GluN2B ratio in neurons of the mouse basal and lateral amygdala inhibits the modification of an existing fear memory trace. J Neurosci 36:9490–9504Google Scholar
  93. 93.
    den Hartog CR, Beckley JT, Smothers TC, Lench DH, Holseberg ZL, Fedarovich H, Gilstrap MJ, Homanics GE, Woodward JJ (2013) Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors. PLoS ONE 8:e80541Google Scholar
  94. 94.
    Mellone M, Stanic J, Hernandez LF, Iglesias E, Zianni E, Longhi A, Prigent A, Picconi B, Calabresi P, Hirsch EC, Obeso JA, Di Luca M, Gardoni F (2015) NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced dyskinesias: from experimental models to patients. Front Cell Neurosci 9:245Google Scholar
  95. 95.
    Goodfellow MJ, Abdulla KA, Lindquist DH (2016) Neonatal ethanol exposure impairs trace fear conditioning and alters NMDA receptor subunit expression in adult male and female rats. Alcohol Clin Exp Res 40:309–318Google Scholar
  96. 96.
    Cercato MC, Colettis N, Snitcofsky M, Aguirre AI, Kornisiuk EE, Baez MV, Jerusalinsky DA (2014) Hippocampal NMDA receptors and the previous experience effect on memory. J Physiol Paris 108:263–269Google Scholar

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Authors and Affiliations

  1. 1.Université de Picardie Jules Verne, INSERM U1247 Research Group on Alcohol & Pharmacodependences (GRAP) – CURSAmiens Cedex 1France

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