Skip to main content
SpringerLink
Log in

Cocaine-Induced Changes in NMDA Receptor Signaling

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Addictive states are often thought to rely on lasting modification of signaling at relevant synapses. A long-standing theory posits that activity at N-methyl-d-aspartate receptors (NMDARs) is a critical component of long-term synaptic plasticity in many brain areas. Indeed, NMDAR signaling has been found to play a role in the etiology of addictive states, in particular, following cocaine exposure. However, no consensus is apparent with respect to the specific effects of cocaine exposure on NMDARs. Part of the difficulty lies in the fact that NMDARs interact extensively with multiple membrane proteins and intracellular signaling cascades. This allows for highly heterogeneous patterns of NMDAR regulation by cocaine in distinct brain regions and at distinct synapses. The picture is further complicated by findings that cocaine effects on NMDARs are sensitive to the behavioral history of cocaine exposure such as the mode of cocaine administration. This review provides a summary of evidence for cocaine-induced changes in NMDAR expression, cocaine-induced alterations in NMDAR function, and cocaine effects on NMDAR control of intracellular signaling cascades.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496

    PubMed  CAS  PubMed Central  Google Scholar 

  2. Schuler T, Mesic I, Madry C, Bartholomaus I, Laube B (2008) Formation of NR1/NR2 and NR1/NR3 heterodimers constitutes the initial step in N-methyl-d-aspartate receptor assembly. J Biol Chem 283(1):37–46

    PubMed  Google Scholar 

  3. Tong G, Takahashi H, Tu S, Shin Y, Talantova M, Zago W, Xia P, Nie Z, Goetz T, Zhang D, Lipton SA, Nakanishi N (2008) Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons. J Neurophysiol 99(1):122–132

    PubMed  CAS  Google Scholar 

  4. Al-Hallaq RA, Conrads TP, Veenstra TD, Wenthold RJ (2007) NMDA di-heteromeric receptor populations and associated proteins in rat hippocampus. J Neurosci 27(31):8334–8343

    PubMed  CAS  PubMed Central  Google Scholar 

  5. Dunah AW, Standaert DG (2003) Subcellular segregation of distinct heteromeric NMDA glutamate receptors in the striatum. J Neurochem 85(4):935–943

    PubMed  CAS  Google Scholar 

  6. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (1994) Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368(6467):144–147

    PubMed  CAS  Google Scholar 

  7. Tovar KR, McGinley MJ, Westbrook GL (2013) Triheteromeric NMDA receptors at hippocampal synapses. J Neurosci 33(21):9150–9160

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Tovar KR, Westbrook GL (1999) The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci 19(10):4180–4188

    PubMed  CAS  Google Scholar 

  9. Brothwell SL, Barber JL, Monaghan DT, Jane DE, Gibb AJ, Jones S (2008) NR2B- and NR2D-containing synaptic NMDA receptors in developing rat substantia nigra pars compacta dopaminergic neurones. J Physiol 586(3):739–750

    PubMed  CAS  PubMed Central  Google Scholar 

  10. Logan SM, Partridge JG, Matta JA, Buonanno A, Vicini S (2007) Long-lasting NMDA receptor-mediated EPSCs in mouse striatal medium spiny neurons. J Neurophysiol 98(5):2693–2704

    PubMed  CAS  Google Scholar 

  11. Oliva C, Escobedo P, Astorga C, Molina C, Sierralta J (2012) Role of the MAGUK protein family in synapse formation and function. Dev Neurobiol 72(1):57–72

    PubMed  CAS  Google Scholar 

  12. Chen B-S, Roche KW (2007) Regulation of NMDA receptors by phosphorylation. Neuropharmacology 53(3):362–368

    PubMed  PubMed Central  Google Scholar 

  13. Brackett RL, Pouw B, Blyden JF, Nour M, Matsumoto RR (2000) Prevention of cocaine-induced convulsions and lethality in mice: effectiveness of targeting different sites on the NMDA receptor complex. Neuropharmacology 39(3):407–418

    PubMed  CAS  Google Scholar 

  14. Pulvirenti L, Berrier R, Kreifeldt M, Koob GF (1994) Modulation of locomotor activity by NMDA receptors in the nucleus accumbens core and shell regions of the rat. Brain Res 664(1–2):231–236

    PubMed  CAS  Google Scholar 

  15. Pulvirenti L, Swerdlow NR, Koob GF (1991) Nucleus accumbens NMDA antagonist decreases locomotor activity produced by cocaine, heroin or accumbens dopamine, but not caffeine. Pharmacol Biochem Behav 40(4):841–845

    PubMed  CAS  Google Scholar 

  16. Uzbay IT, Wallis CJ, Lal H, Forster MJ (2000) Effects of NMDA receptor blockers on cocaine-stimulated locomotor activity in mice. Behav Brain Res 108(1):57–61

    PubMed  CAS  Google Scholar 

  17. Witkin JM (1993) Blockade of the locomotor stimulant effects of cocaine and methamphetamine by glutamate antagonists. Life Sci 53(24):PL405–PL410

    PubMed  CAS  Google Scholar 

  18. Karler R, Calder LD, Chaudhry IA, Turkanis SA (1989) Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801. Life Sci 45(7):599–606

    PubMed  CAS  Google Scholar 

  19. Li Y, Hu XT, Berney TG, Vartanian AJ, Stine CD, Wolf ME, White FJ (1999) Both glutamate receptor antagonists and prefrontal cortex lesions prevent induction of cocaine sensitization and associated neuroadaptations. Synapse 34(3):169–180

    PubMed  CAS  Google Scholar 

  20. Wolf ME, Jeziorski M (1993) Coadministration of MK-801 with amphetamine, cocaine or morphine prevents rather than transiently masks the development of behavioral sensitization. Brain Res 613(2):291–294

    PubMed  CAS  Google Scholar 

  21. Hyytia P, Backstrom P, Liljequist S (1999) Site-specific NMDA receptor antagonists produce differential effects on cocaine self-administration in rats. Eur J Pharmacol 378(1):9–16

    PubMed  CAS  Google Scholar 

  22. Pierce RC, Meil WM, Kalivas PW (1997) The NMDA antagonist, dizocilpine, enhances cocaine reinforcement without influencing mesoaccumbens dopamine transmission. Psychopharmacology (Berl) 133(2):188–195

    CAS  Google Scholar 

  23. Pulvirenti L, Balducci C, Koob GF (1997) Dextromethorphan reduces intravenous cocaine self-administration in the rat. Eur J Pharmacol 321(3):279–283

    PubMed  CAS  Google Scholar 

  24. Rodriguez-Borrero E, Bernardo Colon A, Burgos-Martir MA, Alvarez Carillo JE, del Campo YE, Abella-Ramirez C, Maldonado-Vlaar CS (2006) NMDA antagonist AP-5 increase environmentally induced cocaine-conditioned locomotion within the nucleus accumbens. Pharmacol Biochem Behav 85(1):178–184

    PubMed  CAS  Google Scholar 

  25. Carey RJ, Dai H, Krost M, Huston JP (1995) The NMDA receptor and cocaine: evidence that MK-801 can induce behavioral sensitization effects. Pharmacol Biochem Behav 51(4):901–908

    PubMed  CAS  Google Scholar 

  26. Criswell HE, Johnson KB, Mueller RA, Breese GR (1993) Evidence for involvement of brain dopamine and other mechanisms in the behavioral action of the N-methyl-d-aspartic acid antagonist MK-801 in control and 6-hydroxydopamine-lesioned rats. J Pharmacol Exp Ther 265(2):1001–1010

    PubMed  CAS  Google Scholar 

  27. Wolf ME, Khansa MR (1991) Repeated administration of MK-801 produces sensitization to its own locomotor stimulant effects but blocks sensitization to amphetamine. Brain Res 562(1):164–168

    PubMed  CAS  Google Scholar 

  28. Allen RM (2014) Continuous exposure to dizocilpine facilitates escalation of cocaine consumption in male Sprague–Dawley rats. Drug Alcohol Depend 134:38–43

    PubMed  CAS  Google Scholar 

  29. Ranaldi R, French E, Roberts DC (1996) Systemic pretreatment with MK-801 (dizocilpine) increases breaking points for self-administration of cocaine on a progressive-ratio schedule in rats. Psychopharmacology (Berl) 128(1):83–88

    CAS  Google Scholar 

  30. Engblom D, Bilbao A, Sanchis-Segura C, Dahan L, Perreau-Lenz S, Balland B, Parkitna JR, Luján R, Halbout B, Mameli M (2008) Glutamate receptors on dopamine neurons control the persistence of cocaine seeking. Neuron 59(3):497–508

    PubMed  CAS  Google Scholar 

  31. Heusner C, Palmiter R (2005) Expression of mutant NMDA receptors in dopamine D1 receptor-containing cells prevents cocaine sensitization and decreases cocaine preference. J Neurosci 25(28):6651–6657

    PubMed  CAS  Google Scholar 

  32. Zweifel LS, Argilli E, Bonci A, Palmiter RD (2008) Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors. Neuron 59(3):486–496

    PubMed  CAS  PubMed Central  Google Scholar 

  33. Luo Y, Good CH, Diaz-Ruiz O, Zhang Y, Hoffman AF, Shan L, Kuang SY, Malik N, Chefer VI, Tomac AC, Lupica CR, Backman CM (2010) NMDA receptors on non-dopaminergic neurons in the VTA support cocaine sensitization. PLoS One 5(8):e12141

    PubMed  PubMed Central  Google Scholar 

  34. Cornish JL, Duffy P, Kalivas PW (1999) A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93(4):1359–1367

    PubMed  CAS  Google Scholar 

  35. Famous KR, Schmidt HD, Pierce RC (2007) When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat. Neurosci Lett 420(2):169–173

    PubMed  CAS  PubMed Central  Google Scholar 

  36. Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22(7):2916–2925

    PubMed  CAS  Google Scholar 

  37. Carr DB, Kalivas PW (2008) Confused about NMDA and addiction? Targeted knockouts provide answers and new questions. Neuron 59(3):353–355

    PubMed  CAS  Google Scholar 

  38. Schmidt HD, Pierce RC (2010) Cocaine-induced neuroadaptations in glutamate transmission. Ann N Y Acad Sci 1187(1):35–75

    PubMed  CAS  Google Scholar 

  39. Wolf ME (1998) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog Neurobiol 54(6):679–720

    PubMed  CAS  Google Scholar 

  40. Fitzgerald LW, Ortiz J, Hamedani AG, Nestler EJ (1996) Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. J Neurosci 16(1):274–282

    PubMed  CAS  Google Scholar 

  41. Le Greves P, Zhou Q, Huang W, Nyberg F (2002) Effect of combined treatment with nandrolone and cocaine on the NMDA receptor gene expression in the rat nucleus accumbens and periaqueductal gray. Acta Psychiatr Scand 106(Suppl 412):129–132

    Google Scholar 

  42. Yamaguchi M, Suzuki T, Abe S, Hori T, Kurita H, Asada T, Okado N, Arai H (2002) Repeated cocaine administration differentially affects NMDA receptor subunit (NR1, NR2A-C) mRNAs in rat brain. Synapse 46(3):157–169

    PubMed  CAS  Google Scholar 

  43. Crespo JA, Oliva JM, Ghasemzadeh MB, Kalivas PW, Ambrosio E (2002) Neuroadaptive changes in NMDAR1 gene expression after extinction of cocaine self-administration. Ann N Y Acad Sci 965:78–91

    PubMed  CAS  Google Scholar 

  44. Ghasemzadeh MB, Mueller C, Vasudevan P (2009) Behavioral sensitization to cocaine is associated with increased glutamate receptor trafficking to the postsynaptic density after extended withdrawal period. Neuroscience 159(1):414–426

    PubMed  CAS  Google Scholar 

  45. Schumann J, Yaka R (2009) Prolonged withdrawal from repeated noncontingent cocaine exposure increases NMDA receptor expression and ERK activity in the nucleus accumbens. J Neurosci 29(21):6955–6963

    PubMed  CAS  Google Scholar 

  46. Yamamoto DJ, Zahniser NR (2012) Differences in rat dorsal striatal NMDA and AMPA receptors following acute and repeated cocaine-induced locomotor activation. PLoS One 7(5):e37673

    PubMed  CAS  PubMed Central  Google Scholar 

  47. Loftis JM, Janowsky A (2000) Regulation of NMDA receptor subunits and nitric oxide synthase expression during cocaine withdrawal. J Neurochem 75(5):2040–2050

    PubMed  CAS  Google Scholar 

  48. Churchill L, Swanson CJ, Urbina M, Kalivas PW (1999) Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization. J Neurochem 72(6):2397–2403

    PubMed  CAS  Google Scholar 

  49. Zhang X, Lee TH, Davidson C, Lazarus C, Wetsel WC, Ellinwood EH (2007) Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors. Neuropsychopharmacology 32(2):377–387

    PubMed  CAS  Google Scholar 

  50. Ferrario CR, Li X, Wang X, Reimers JM, Uejima JL, Wolf ME (2010) The role of glutamate receptor redistribution in locomotor sensitization to cocaine. Neuropsychopharmacology 35(3):818–833

    PubMed  CAS  PubMed Central  Google Scholar 

  51. Scheggi S, Mangiavacchi S, Masi F, Gambarana C, Tagliamonte A, De Montis MG (2002) Dizocilpine infusion has a different effect in the development of morphine and cocaine sensitization: behavioral and neurochemical aspects. Neuroscience 109(2):267–274

    PubMed  CAS  Google Scholar 

  52. Lu L, Grimm JW, Shaham Y, Hope BT (2003) Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats. J Neurochem 85(6):1604–1613

    PubMed  CAS  Google Scholar 

  53. Ortinski PI, Turner JR, Pierce RC (2013) Extrasynaptic targeting of NMDA receptors following D1 dopamine receptor activation and cocaine self-administration. J Neurosci 33(22):9451–9461

    PubMed  CAS  PubMed Central  Google Scholar 

  54. Ben-Shahar O, Keeley P, Cook M, Brake W, Joyce M, Nyffeler M, Heston R, Ettenberg A (2007) Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine. Brain Res 1131:220–228

    PubMed  CAS  PubMed Central  Google Scholar 

  55. Self D, Choi K, Simmons D, Walker J, Smagula CS (2004) Extinction training regulates neuroadaptive responses to withdrawal from chronic cocaine self-administration. Learn Mem 11(5):648–657

    PubMed  PubMed Central  Google Scholar 

  56. Ferrario CR, Goussakov I, Stutzmann GE, Wolf ME (2012) Withdrawal from cocaine self-administration alters NMDA receptor-mediated Ca2+ entry in nucleus accumbens dendritic spines. PLoS One 7(8):e40898

    PubMed  CAS  PubMed Central  Google Scholar 

  57. Ghasemzadeh MB, Vasudevan P, Giles C, Purgianto A, Seubert C, Mantsch JR (2011) Glutamatergic plasticity in medial prefrontal cortex and ventral tegmental area following extended-access cocaine self-administration. Brain Res 1413:60–71

    PubMed  CAS  PubMed Central  Google Scholar 

  58. Itzhak Y, Martin JL (2000) Cocaine-induced kindling is associated with elevated NMDA receptor binding in discrete mouse brain regions. Neuropharmacology 39(1):32–39

    PubMed  CAS  Google Scholar 

  59. Loftis JM, Janowsky A (2002) Cocaine treatment- and withdrawal-induced alterations in the expression and serine phosphorylation of the NR1 NMDA receptor subunit. Psychopharmacology (Berl) 164(4):349–359

    CAS  Google Scholar 

  60. Izawa R, Jaber M, Deroche-Gamonet V, Sillaber I, Kellendonk C, Le Moal M, Tronche F, Piazza PV (2006) Gene expression regulation following behavioral sensitization to cocaine in transgenic mice lacking the glucocorticoid receptor in the brain. Neuroscience 137(3):915–924

    PubMed  CAS  Google Scholar 

  61. Szumlinski KK, Herrick-Davis K, Teitler M, Maisonneuve IM, Glick SD (2000) Behavioural sensitization to cocaine is dissociated from changes in striatal NMDA receptor levels. Neuroreport 11(12):2785–2788

    PubMed  CAS  Google Scholar 

  62. Itzhak Y (1994) Modulation of the PCP/NMDA receptor complex and sigma binding sites by psychostimulants. Neurotoxicol Teratol 16(4):363–368

    PubMed  CAS  Google Scholar 

  63. Itzhak Y, Stein I (1992) Sensitization to the toxic effects of cocaine in mice is associated with the regulation of N-methyl-d-aspartate receptors in the cortex. J Pharmacol Exp Ther 262(2):464–470

    PubMed  CAS  Google Scholar 

  64. Bhargava HN, Kumar S (1999) Sensitization to the locomotor stimulant effect of cocaine modifies the binding of [3H]MK-801 to brain regions and spinal cord of the mouse. Gen Pharmacol 32(3):359–363

    PubMed  CAS  Google Scholar 

  65. Ghasemzadeh MB, Vasudevan P, Mueller C (2009) Locomotor sensitization to cocaine is associated with distinct pattern of glutamate receptor trafficking to the postsynaptic density in prefrontal cortex: early versus late withdrawal effects. Pharmacol Biochem Behav 92(3):383–392

    PubMed  CAS  Google Scholar 

  66. Ortiz JG, Gonzalez-Cabrera S, Rubio-Davila M, Tirado-Costacamps A, Vazquez-Torres R, Berrios-Cartagena N, Silva WI, Jimenez-Rivera CA (2006) AMPA and NMDA receptors in P2 fractions of cocaine and cocaine-prazosin-treated rats. Ann N Y Acad Sci 1074:403–410

    PubMed  CAS  Google Scholar 

  67. Turchan J, Maj M, Przewlocka B (2003) The effect of drugs of abuse on NMDAR1 receptor expression in the rat limbic system. Drug Alcohol Depend 72(2):193–196

    PubMed  CAS  Google Scholar 

  68. Lu L, Dempsey J, Shaham Y, Hope BT (2005) Differential long-term neuroadaptations of glutamate receptors in the basolateral and central amygdala after withdrawal from cocaine self-administration in rats. J Neurochem 94(1):161–168

    PubMed  CAS  Google Scholar 

  69. Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30(2):215–238

    PubMed  CAS  Google Scholar 

  70. Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65(1):7–19

    PubMed  CAS  PubMed Central  Google Scholar 

  71. Lasseter HC, Xie X, Ramirez DR, Fuchs RA (2010) Sub-region specific contribution of the ventral hippocampus to drug context-induced reinstatement of cocaine-seeking behavior in rats. Neuroscience 171(3):830–839

    PubMed  CAS  PubMed Central  Google Scholar 

  72. Sun W, Rebec GV (2003) Lidocaine inactivation of ventral subiculum attenuates cocaine-seeking behavior in rats. J Neurosci 23(32):10258–10264

    PubMed  CAS  Google Scholar 

  73. Phillips AG, Ahn S, Howland JG (2003) Amygdalar control of the mesocorticolimbic dopamine system: parallel pathways to motivated behavior. Neurosci Biobehav Rev 27(6):543–554

    PubMed  CAS  Google Scholar 

  74. Tang WX, Fasulo WH, Mash DC, Hemby SE (2003) Molecular profiling of midbrain dopamine regions in cocaine overdose victims. J Neurochem 85(4):911–924

    PubMed  CAS  PubMed Central  Google Scholar 

  75. Chen BT, Bowers MS, Martin M, Hopf FW, Guillory AM, Carelli RM, Chou JK, Bonci A (2008) Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA. Neuron 59(2):288–297

    PubMed  CAS  PubMed Central  Google Scholar 

  76. Dumont EC, Mark GP, Mader S, Williams JT (2005) Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis. Nat Neurosci 8(4):413–414

    PubMed  CAS  PubMed Central  Google Scholar 

  77. Dobi A, Seabold GK, Christensen CH, Bock R, Alvarez VA (2011) Cocaine-induced plasticity in the nucleus accumbens is cell specific and develops without prolonged withdrawal. J Neurosci 31(5):1895–1904

    PubMed  CAS  PubMed Central  Google Scholar 

  78. Kourrich S, Rothwell PE, Klug JR, Thomas MJ (2007) Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens. J Neurosci 27(30):7921–7928

    PubMed  CAS  Google Scholar 

  79. Ortinski PI, Vassoler FM, Carlson GC, Pierce RC (2012) Temporally dependent changes in cocaine-induced synaptic plasticity in the nucleus accumbens shell are reversed by D1-like dopamine receptor stimulation. Neuropsychopharmacology 37(7):1671–1682

    PubMed  CAS  PubMed Central  Google Scholar 

  80. Otaka M, Ishikawa M, Lee BR, Liu L, Neumann PA, Cui R, Huang YH, Schluter OM, Dong Y (2013) Exposure to cocaine regulates inhibitory synaptic transmission in the nucleus accumbens. J Neurosci 33(16):6753–6758

    PubMed  CAS  PubMed Central  Google Scholar 

  81. Schumann J, Matzner H, Michaeli A, Yaka R (2009) NR2A/B-containing NMDA receptors mediate cocaine-induced synaptic plasticity in the VTA and cocaine psychomotor sensitization. Neurosci Lett 461(2):159–162

    PubMed  CAS  Google Scholar 

  82. Borgland SL, Malenka RC, Bonci A (2004) Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: electrophysiological and behavioral correlates in individual rats. J Neurosci 24(34):7482–7490

    Google Scholar 

  83. Thomas MJ, Beurrier C, Bonci A, Malenka RC (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci 4(12):1217–1223

    PubMed  CAS  Google Scholar 

  84. Zhang XF, Hu XT, White FJ, Wolf ME (1997) Increased responsiveness of ventral tegmental area dopamine neurons to glutamate after repeated administration of cocaine or amphetamine is transient and selectively involves AMPA receptors. J Pharmacol Exp Ther 281(2):699–706

    PubMed  CAS  Google Scholar 

  85. Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A (2012) Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76(4):790–803

    PubMed  CAS  PubMed Central  Google Scholar 

  86. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12(3):529–540

    PubMed  CAS  Google Scholar 

  87. Sucher NJ, Akbarian S, Chi CL, Leclerc CL, Awobuluyi M, Deitcher DL, Wu MK, Yuan JP, Jones EG, Lipton SA (1995) Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci 15(10):6509–6520

    PubMed  CAS  Google Scholar 

  88. Bloomfield C, O'Donnell P, French SJ, Totterdell S (2007) Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits. Neuroscience 150(3):639–646

    PubMed  CAS  PubMed Central  Google Scholar 

  89. Wee KS, Zhang Y, Khanna S, Low CM (2008) Immunolocalization of NMDA receptor subunit NR3B in selected structures in the rat forebrain, cerebellum, and lumbar spinal cord. J Comp Neurol 509(1):118–135

    PubMed  CAS  Google Scholar 

  90. Yuan T, Mameli M, O’Connor EC, Dey PN, Verpelli C, Sala C, Perez-Otano I, Luscher C, Bellone C (2013) Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors. Neuron 80(4):1025–1038

    PubMed  CAS  Google Scholar 

  91. Brown TE, Lee BR, Mu P, Ferguson D, Dietz D, Ohnishi YN, Lin Y, Suska A, Ishikawa M, Huang YH, Shen H, Kalivas PW, Sorg BA, Zukin RS, Nestler EJ, Dong Y, Schluter OM (2011) A silent synapse-based mechanism for cocaine-induced locomotor sensitization. J Neurosci 31(22):8163–8174

    PubMed  CAS  PubMed Central  Google Scholar 

  92. Huang YH, Lin Y, Mu P, Lee BR, Brown TE, Wayman G, Marie H, Liu W, Yan Z, Sorg BA (2009) In vivo cocaine experience generates silent synapses. Neuron 63(1):40–47

    PubMed  CAS  PubMed Central  Google Scholar 

  93. Groc L, Heine M, Cousins SL, Stephenson FA, Lounis B, Cognet L, Choquet D (2006) NMDA receptor surface mobility depends on NR2A-2B subunits. Proc Natl Acad Sci U S A 103(49):18769–18774

    PubMed  CAS  PubMed Central  Google Scholar 

  94. Isaac JT (2003) Postsynaptic silent synapses: evidence and mechanisms. Neuropharmacology 45(4):450–460

    PubMed  CAS  Google Scholar 

  95. Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162(8):1403–1413

    PubMed  Google Scholar 

  96. Cepeda C, Buchwald NA, Levine MS (1993) Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated. Proc Natl Acad Sci U S A 90(20):9576–9580

    PubMed  CAS  PubMed Central  Google Scholar 

  97. Cepeda C, Levine MS (1998) Dopamine and N-methyl-d-aspartate receptor interactions in the neostriatum. Dev Neurosci 20(1):1–18

    PubMed  CAS  Google Scholar 

  98. Chergui K, Lacey MG (1999) Modulation by dopamine D1-like receptors of synaptic transmission and NMDA receptors in rat nucleus accumbens is attenuated by the protein kinase C inhibitor Ro 32-0432. Neuropharmacology 38(2):223–231

    PubMed  CAS  Google Scholar 

  99. Flores-Hernández J, Cepeda C, Hernández-Echeagaray E, Calvert C, Jokel E, Fienberg A, Greengard P, Levine M (2002) Dopamine enhancement of NMDA currents in dissociated medium-sized striatal neurons: role of D1 receptors and DARPP-32. J Neurophysiol 88(6):3010–3020

    PubMed  Google Scholar 

  100. Harvey J, Lacey MG (1997) A postsynaptic interaction between dopamine D1 and NMDA receptors promotes presynaptic inhibition in the rat nucleus accumbens via adenosine release. J Neurosci 17(14):5271–5280

    PubMed  CAS  Google Scholar 

  101. Beurrier C, Malenka RC (2002) Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine. J Neurosci 22(14):5817–5822

    PubMed  CAS  Google Scholar 

  102. Schilström B, Yaka R, Argilli E, Suvarna N, Schumann J, Chen B, Carman M, Singh V, Mailliard W, Ron D, Bonci A (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci 26(33):8549–8558

    PubMed  Google Scholar 

  103. Madhavan A, Argilli E, Bonci A, Whistler JL (2013) Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic synaptic potentiation in the ventral tegmental area. J Neurosci 33(30):12329–12336

    PubMed  CAS  PubMed Central  Google Scholar 

  104. Yang SN (2000) Sustained enhancement of AMPA receptor- and NMDA receptor-mediated currents induced by dopamine D1/D5 receptor activation in the hippocampus: an essential role of postsynaptic Ca2+. Hippocampus 10(1):57–63

    PubMed  CAS  Google Scholar 

  105. Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25(3):515–532

    PubMed  CAS  Google Scholar 

  106. Kalivas PW, O'Brien C (2008) Drug addiction as a pathology of staged neuroplasticity. Neuropsychopharmacology 33(1):166–180

    PubMed  CAS  Google Scholar 

  107. Lobo MK, Nestler EJ (2011) The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Front Neuroanat 5:41

    PubMed  PubMed Central  Google Scholar 

  108. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78(1):189–225

    PubMed  CAS  Google Scholar 

  109. Mattson BJ, Bossert JM, Simmons DE, Nozaki N, Nagarkar D, Kreuter JD, Hope BT (2005) Cocaine-induced CREB phosphorylation in nucleus accumbens of cocaine-sensitized rats is enabled by enhanced activation of extracellular signal-related kinase, but not protein kinase A. J Neurochem 95(5):1481–1494

    PubMed  CAS  Google Scholar 

  110. Pierce RC, Pierce-Bancroft AF, Prasad BM (1999) Neurotrophin-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/Mitogen-activated protein kinase signal transduction cascade. J Neurosci 19(19):8685–8695

    PubMed  CAS  Google Scholar 

  111. Valjent E, Corvol JC, Pages C, Besson MJ, Maldonado R, Caboche J (2000) Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J Neurosci 20(23):8701–8709

    PubMed  CAS  Google Scholar 

  112. Zachariou V, Sgambato-Faure V, Sasaki T, Svenningsson P, Berton O, Fienberg AA, Nairn AC, Greengard P, Nestler EJ (2006) Phosphorylation of DARPP-32 at threonine-34 is required for cocaine action. Neuropsychopharmacology 31(3):555–562

    PubMed  CAS  Google Scholar 

  113. Zhang Y, Svenningsson P, Picetti R, Schlussman SD, Nairn AC, Ho A, Greengard P, Kreek MJ (2006) Cocaine self-administration in mice is inversely related to phosphorylation at Thr34 (protein kinase A site) and Ser130 (kinase CK1 site) of DARPP-32. J Neurosci 26(10):2645–2651

    PubMed  CAS  Google Scholar 

  114. Li Y-C, Liu G, Hu J-L, Gao W-J, Huang Y-Q (2010) Dopamine D1 receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons. J Neurochem 114(1):62–73

    PubMed  CAS  Google Scholar 

  115. Sarantis K, Matsokis N, Angelatou F (2009) Synergistic interactions of dopamine D1 and glutamate NMDA receptors in rat hippocampus and prefrontal cortex: involvement of ERK1/2 signaling. Neuroscience 163(4):1135–1145

    PubMed  CAS  Google Scholar 

  116. Nishi A, Kuroiwa M, Shuto T (2011) Mechanisms for the modulation of dopamine D(1) receptor signaling in striatal neurons. Front Neuroanat 5:43

    PubMed  CAS  PubMed Central  Google Scholar 

  117. Pascoli V, Besnard A, Herve D, Pages C, Heck N, Girault JA, Caboche J, Vanhoutte P (2011) Cyclic adenosine monophosphate-independent tyrosine phosphorylation of NR2B mediates cocaine-induced extracellular signal-regulated kinase activation. Biol Psychiatry 69(3):218–227

    PubMed  CAS  Google Scholar 

  118. Halpain S, Girault JA, Greengard P (1990) Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices. Nature 343(6256):369–372

    PubMed  CAS  Google Scholar 

  119. Nairn AC, Svenningsson P, Nishi A, Fisone G, Girault JA, Greengard P (2004) The role of DARPP-32 in the actions of drugs of abuse. Neuropharmacology 47(Suppl 1):14–23

    PubMed  CAS  Google Scholar 

  120. Nishi A, Snyder GL, Nairn AC, Greengard P (1999) Role of calcineurin and protein phosphatase-2A in the regulation of DARPP-32 dephosphorylation in neostriatal neurons. J Neurochem 72(5):2015–2021

    PubMed  CAS  Google Scholar 

  121. Jenab S, Festa ED, Nazarian A, Wu HB, Sun WL, Hazim R, Russo SJ, Quinones-Jenab V (2005) Cocaine induction of ERK proteins in dorsal striatum of Fischer rats. Brain Res Mol Brain Res 142(2):134–138

    PubMed  CAS  Google Scholar 

  122. Jiao H, Zhang L, Gao F, Lou D, Zhang J, Xu M (2007) Dopamine D(1) and D(3) receptors oppositely regulate NMDA- and cocaine-induced MAPK signaling via NMDA receptor phosphorylation. J Neurochem 103(2):840–848

    PubMed  CAS  Google Scholar 

  123. Lu L, Koya E, Zhai H, Hope BT, Shaham Y (2006) Role of ERK in cocaine addiction. Trends Neurosci 29(12):695–703

    PubMed  CAS  Google Scholar 

  124. Sun WL, Zhou L, Hazim R, Quinones-Jenab V, Jenab S (2008) Effects of dopamine and NMDA receptors on cocaine-induced Fos expression in the striatum of Fischer rats. Brain Res 1243:1–9

    PubMed  CAS  PubMed Central  Google Scholar 

  125. Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, Girault JA (2008) Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 28(22):5671–5685

    PubMed  CAS  Google Scholar 

  126. Gangarossa G, Espallergues J, de Kerchove d’Exaerde A, El Mestikawy S, Gerfen CR, Herve D, Girault JA, Valjent E (2013) Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens. Front Neural Circ 7:22

    Google Scholar 

  127. Gerfen CR, Paletzki R, Worley P (2008) Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase. J Neurosci 28(28):7113–7120

    PubMed  CAS  PubMed Central  Google Scholar 

  128. Cestari V, Rossi-Arnaud C, Saraulli D, Costanzi M (2013) The MAP(K) of fear: from memory consolidation to memory extinction. Brain Res Bull. doi:10.1016/j.brainresbull.2013.09.007

  129. Berretta S, Robertson HA, Graybiel AM (1992) Dopamine and glutamate agonists stimulate neuron-specific expression of Fos-like protein in the striatum. J Neurophysiol 68(3):767–777

    PubMed  CAS  Google Scholar 

  130. Koya E, Cruz FC, Ator R, Golden SA, Hoffman AF, Lupica CR, Hope BT (2012) Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization. Nat Neurosci 15(11):1556–1562

    PubMed  CAS  PubMed Central  Google Scholar 

  131. Torres G, Rivier C (1993) Cocaine-induced expression of striatal c-fos in the rat is inhibited by NMDA receptor antagonists. Brain Res Bull 30(1–2):173–176

    PubMed  CAS  Google Scholar 

  132. Rani CS, Qiang M, Ticku MK (2005) Potential role of cAMP response element-binding protein in ethanol-induced N-methyl-d-aspartate receptor 2B subunit gene transcription in fetal mouse cortical cells. Mol Pharmacol 67(6):2126–2136

    PubMed  CAS  Google Scholar 

  133. Suzuki K, Sato M, Morishima Y, Nakanishi S (2005) Neuronal depolarization controls brain-derived neurotrophic factor-induced upregulation of NR2C NMDA receptor via calcineurin signaling. J Neurosci 25(41):9535–9543

    PubMed  CAS  Google Scholar 

  134. Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z (2005) Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J Neurosci 25(23):5488–5501

    PubMed  CAS  Google Scholar 

  135. Ivanov A, Pellegrino C, Rama S, Dumalska I, Salyha Y, Ben-Ari Y, Medina I (2006) Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons. J Physiol 572(Pt 3):789–798

    PubMed  CAS  PubMed Central  Google Scholar 

  136. Karpova A, Mikhaylova M, Bera S, Bar J, Reddy PP, Behnisch T, Rankovic V, Spilker C, Bethge P, Sahin J, Kaushik R, Zuschratter W, Kahne T, Naumann M, Gundelfinger ED, Kreutz MR (2013) Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus. Cell 152(5):1119–1133

    PubMed  CAS  Google Scholar 

  137. Léveillé F, El Gaamouch F, Gouix E, Lecocq M, Lobner D, Nicole O, Buisson A (2008) Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB J 22(12):4258–4271

    PubMed  Google Scholar 

  138. Gladding CM, Raymond LA (2011) Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. Mol Cell Neurosci 48(4):308–320

    Google Scholar 

Download references

Acknowledgments

This work was funded by NIH grant K01DA031747 to PIO.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA

    Pavel I. Ortinski

  2. Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Building 1, Room D-54, Columbia, SC, 29208, USA

    Pavel I. Ortinski

Authors
  1. Pavel I. Ortinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pavel I. Ortinski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortinski, P.I. Cocaine-Induced Changes in NMDA Receptor Signaling. Mol Neurobiol 50, 494–506 (2014). https://doi.org/10.1007/s12035-014-8636-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8636-6

Keywords

Search

Navigation