Molecular Neurobiology

, Volume 36, Issue 3, pp 232–244 | Cite as

Group I mGluRs and Long-Term Depression: Potential Roles in Addiction?

  • Brad A. Grueter
  • Zoé A. McElligott
  • Danny G. Winder


Addiction is an enormous societal problem. A number of recent studies have focused on adaptations at glutamatergic synapses that may play a role in the behavioral responses to drugs of abuse. These studies have largely focused on NMDA receptor-dependent forms of synaptic plasticity such as NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD). A growing body of evidence, however, suggests that metabotropic glutamate receptors (mGluRs) also play important roles in the behavioral responses to drugs of abuse and participate in producing synaptic plasticity at glutamate synapses. In this review, we focus first on the evidence supporting a role for mGluRs in addiction and then on the properties of mGluR-dependent forms of synaptic plasticity, focusing in particular on Gq-linked receptor-induced LTD.


Addiction Group I mGluRs Long-term depression 



This work was supported by NIAAA and NIDA.


  1. 1.
    Adams JP, Sweatt JD (2002) Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol 42:135–163PubMedGoogle Scholar
  2. 2.
    Aiba A, Kano M, Chen C, Stanton ME, Fox GD, Herrup K, Zwingman TA, Tonegawa S (1994) Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell 79:377–388PubMedGoogle Scholar
  3. 3.
    Antar LN, Afroz R, Dictenberg JB, Carroll RC, Bassell GJ (2004) Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J Neurosci 24:2648–2655PubMedGoogle Scholar
  4. 4.
    Anwyl R (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev 29:83–120PubMedGoogle Scholar
  5. 5.
    Backstrom P, Hyytia P (2005) Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology 31:778–786Google Scholar
  6. 6.
    Baker DA, Shen H, Kalivas PW (2002) Cystine/glutamate exchange serves as the source for extracellular glutamate: modifications by repeated cocaine administration. Amino Acids 23:161–162PubMedGoogle Scholar
  7. 7.
    Balazs R, Miller S, Romano C, de Vries A, Chun Y, Cotman CW (1997) Metabotropic glutamate receptor mGluR5 in astrocytes: pharmacological properties and agonist regulation. J Neurochem 69:151–163PubMedCrossRefGoogle Scholar
  8. 8.
    Bear MF, Singer W (1986) Modulation of visual cortical plasticity by acetylcholine and noradrenaline. Nature 320:172–176PubMedGoogle Scholar
  9. 9.
    Bellone C, Luscher C (2005) mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors. Eur J Neurosci 21:1280–1288PubMedGoogle Scholar
  10. 10.
    Bellone C, Luscher C (2006) Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression. Nat Neurosci 9:636–641PubMedGoogle Scholar
  11. 11.
    Beurrier C, Malenka RC (2002) Enhanced inhibition of synaptic transmission by dopamine in the nucleus accumbens during behavioral sensitization to cocaine. J Neurosci 22:5817–5822PubMedGoogle Scholar
  12. 12.
    Bolshakov VY, Siegelbaum SA (1994) Postsynaptic induction and presynaptic expression of hippocampal long-term depression. Science 264:1148–1152PubMedGoogle Scholar
  13. 13.
    Bolshakov VY, Carboni L, Cobb MH, Siegelbaum SA, Belardetti F (2000) Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3-CA1 synapses. Nat Neurosci 3:1107–1112PubMedGoogle Scholar
  14. 14.
    Borges K, Dingledine R (1998) AMPA receptors: molecular and functional diversity. Prog Brain Res 116:153–170PubMedCrossRefGoogle Scholar
  15. 15.
    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 24:7482–7490PubMedGoogle Scholar
  16. 16.
    Brakeman PR, Lanahan AA, O’Brien R, Roche K, Barnes CA, Huganir RL, Worley PF (1997) Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386:284–288PubMedGoogle Scholar
  17. 17.
    Chao SZ, Ariano MA, Peterson DA, Wolf ME (2002) D1 dopamine receptor stimulation increases GluR1 surface expression in nucleus accumbens neurons. J Neurochem 83:704–712PubMedGoogle Scholar
  18. 18.
    Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH (2001) MAP kinases. Chem Rev 101:2449–2476PubMedGoogle Scholar
  19. 19.
    Chiamulera C, Epping-Jordan MP, Zocchi A, Marcon C, Cottiny C, Tacconi S, Corsi M, Orzi F, Conquet F (2001) Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat Neurosci 4:873–874PubMedGoogle Scholar
  20. 20.
    Choi S, Lovinger DM (1997) Decreased frequency but not amplitude of quantal synaptic responses associated with expression of corticostriatal long-term depression. J Neurosci 17:8613–8620PubMedGoogle Scholar
  21. 21.
    Choi SY, Chang J, Jiang B, Seol GH, Min SS, Han JS, Shin HS, Gallagher M, Kirkwood A (2005) Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex. J Neurosci 25:11433–11443PubMedGoogle Scholar
  22. 22.
    Chung HJ, Steinberg JP, Huganir RL, Linden DJ (2003) Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science 300:1751–1755PubMedGoogle Scholar
  23. 23.
    Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237PubMedGoogle Scholar
  24. 24.
    Coutinho V, Knopfel T (2002) Metabotropic glutamate receptors: electrical and chemical signaling properties. Neuroscientist 8:551–561PubMedGoogle Scholar
  25. 25.
    Delgado JY, O’Dell TJ (2005) Long-term potentiation persists in an occult state following mGluR-dependent depotentiation. Neuropharmacology 48:936–948PubMedGoogle Scholar
  26. 26.
    Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61PubMedGoogle Scholar
  27. 27.
    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 8:413–414PubMedGoogle Scholar
  28. 28.
    Ehrengruber MU, Kato A, Inokuchi K, Hennou S (2004) Homer/Vesl proteins and their roles in CNS neurons. Mol Neurobiol 29:213–227PubMedGoogle Scholar
  29. 29.
    Erb S, Stewart J (1999) A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci 19:RC35PubMedGoogle Scholar
  30. 30.
    Erb S, Salmaso N, Rodaros D, Stewart J (2001) A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl) 158:360–365Google Scholar
  31. 31.
    Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R (2003) PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 6:136–143PubMedGoogle Scholar
  32. 32.
    Faas GC, Adwanikar H, Gereau RWt, Saggau P (2002) Modulation of presynaptic calcium transients by metabotropic glutamate receptor activation: a differential role in acute depression of synaptic transmission and long-term depression. J Neurosci 22:6885–6890PubMedGoogle Scholar
  33. 33.
    Feinmark SJ, Begum R, Tsvetkov E, Goussakov I, Funk CD, Siegelbaum SA, Bolshakov VY (2003) 12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses. J Neurosci 23:11427–11435PubMedGoogle Scholar
  34. 34.
    Fendt M, Schmid S (2002) Metabotropic glutamate receptors are involved in amygdaloid plasticity. Eur J Neurosci 15:1535–1541PubMedGoogle Scholar
  35. 35.
    Fitzjohn SM, Kingston AE, Lodge D, Collingridge GL (1999) DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists. Neuropharmacology 38:1577–1583PubMedGoogle Scholar
  36. 36.
    Fourgeaud L, Mato S, Bouchet D, Hemar A, Worley PF, Manzoni OJ (2004) A single in vivo exposure to cocaine abolishes endocannabinoid-mediated long-term depression in the nucleus accumbens. J Neurosci 24:6939–6945PubMedGoogle Scholar
  37. 37.
    Francesconi W, Cammalleri M, Sanna PP (2004) The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region. Brain Res 1022:12–18PubMedGoogle Scholar
  38. 38.
    Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066PubMedGoogle Scholar
  39. 39.
    Gallagher SM, Daly CA, Bear MF, Huber KM (2004) Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. J Neurosci 24:4859–4864PubMedGoogle Scholar
  40. 40.
    Gerdeman G, Lovinger DM (2001) CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. J Neurophysiol 85:468–471PubMedGoogle Scholar
  41. 41.
    Gerdeman GL, Lovinger DM (2003) Emerging roles for endocannabinoids in long-term synaptic plasticity. Br J Pharmacol 140:781–789PubMedGoogle Scholar
  42. 42.
    Gerdeman GL, Ronesi J, Lovinger DM (2002) Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci 5:446–451PubMedGoogle Scholar
  43. 43.
    Grueter BA, Gosnell HB, Olsen CM, Schramm-Sapyta NL, Nekrasova T, Landreth GE, Winder DG (2006) Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration. J Neurosci 26:3210–3219PubMedGoogle Scholar
  44. 44.
    Gubellini P, Pisani A, Centonze D, Bernardi G, Calabresi P (2004) Metabotropic glutamate receptors and striatal synaptic plasticity: implications for neurological diseases. Prog Neurobiol 74:271–300PubMedGoogle Scholar
  45. 45.
    Gubellini P, Saulle E, Centonze D, Costa C, Tropepi D, Bernardi G, Conquet F, Calabresi P (2003) Corticostriatal LTP requires combined mGluR1 and mGluR5 activation. Neuropharmacology 44:8–16PubMedGoogle Scholar
  46. 46.
    Harvey J, Palmer MJ, Irving AJ, Clarke VR, Collingridge GL (1996) NMDA receptor dependence of mGlu-mediated depression of synaptic transmission in the CA1 region of the rat hippocampus. Br J Pharmacol 119:1239–1247PubMedGoogle Scholar
  47. 47.
    Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86:1009–1031PubMedGoogle Scholar
  48. 48.
    Herzig V, Schmidt WJ (2004) Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine. Neuropharmacology 47:973–984PubMedCrossRefGoogle Scholar
  49. 49.
    Hirono M, Sugiyama T, Kishimoto Y, Sakai I, Miyazawa T, Kishio M, Inoue H, Nakao K, Ikeda M, Kawahara S, Kirino Y, Katsuki M, Horie H, Ishikawa Y, Yoshioka T (2001) Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells. J Biol Chem 276:45236–45242PubMedGoogle Scholar
  50. 50.
    Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108PubMedGoogle Scholar
  51. 51.
    Hou L, Klann E (2004) Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 24:6352–6361PubMedGoogle Scholar
  52. 52.
    Hou L, Antion MD, Hu D, Spencer CM, Paylor R, Klann E (2006) Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51:441–454PubMedGoogle Scholar
  53. 53.
    Hu G, Duffy P, Swanson C, Ghasemzadeh MB, Kalivas PW (1999) The regulation of dopamine transmission by metabotropic glutamate receptors. J Pharmacol Exp Ther 289:412–416PubMedGoogle Scholar
  54. 54.
    Huang CC, Hsu KS (2006) Sustained activation of metabotropic glutamate receptor 5 and protein tyrosine phosphatases mediate the expression of (S)-3,5-dihydroxyphenylglycine-induced long-term depression in the hippocampal CA1 region. J Neurochem 96:179–194PubMedGoogle Scholar
  55. 55.
    Huang CC, You JL, Wu MY, Hsu KS (2004) Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI.Rab5 complex. Potential role in (S)-3,5-dihydroxyphenylglycene-induced long term depression. J Biol Chem 279:12286–12292PubMedGoogle Scholar
  56. 56.
    Huang LQ, Rowan MJ, Anwyl R (1999) Role of protein kinases A and C in the induction of mGluR-dependent long-term depression in the medial perforant path of the rat dentate gyrus in vitro. Neurosci Lett 274:71–74PubMedGoogle Scholar
  57. 57.
    Huber KM, Kayser MS, Bear MF (2000) Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 288:1254–1257PubMedGoogle Scholar
  58. 58.
    Huber KM, Roder JC, Bear MF (2001) Chemical induction of mGluR5- and protein synthesis-dependent long-term depression in hippocampal area CA1. J Neurophysiol 86:321–325PubMedGoogle Scholar
  59. 59.
    Huber KM, Gallagher SM, Warren ST, Bear MF (2002) Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 99:7746–7750PubMedGoogle Scholar
  60. 60.
    Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 29:565–598PubMedGoogle Scholar
  61. 61.
    Iso Y, Grajkowska E, Wroblewski JT, Davis J, Goeders NE, Johnson KM, Sanker S, Roth BL, Tueckmantel W, Kozikowski AP (2006) Synthesis and structure–activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications. J Med Chem 49:1080–1100PubMedGoogle Scholar
  62. 62.
    Ito M (2001) Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195PubMedGoogle Scholar
  63. 63.
    Ito M, Sakurai M, Tongroach P (1982) Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. J Physiol 324:113–134PubMedGoogle Scholar
  64. 64.
    Jia Z, Lu Y, Henderson J, Taverna F, Romano C, Abramow-Newerly W, Wojtowicz JM, Roder J (1998) Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn Mem 5:331–343PubMedGoogle Scholar
  65. 65.
    Ju W, Morishita W, Tsui J, Gaietta G, Deerinck TJ, Adams SR, Garner CC, Tsien RY, Ellisman MH, Malenka RC (2004) Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors. Nat Neurosci 7:244–253PubMedGoogle Scholar
  66. 66.
    Kawasaki H, Fujii H, Gotoh Y, Morooka T, Shimohama S, Nishida E, Hirano T (1999) Requirement for mitogen-activated protein kinase in cerebellar long term depression. J Biol Chem 274:13498–13502PubMedGoogle Scholar
  67. 67.
    Kemp N, Bashir ZI (1999) Induction of LTD in the adult hippocampus by the synaptic activation of AMPA/kainate and metabotropic glutamate receptors. Neuropharmacology 38:495–504PubMedGoogle Scholar
  68. 68.
    Kirkwood A, Rozas C, Kirkwood J, Perez F, Bear MF (1999) Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. J Neurosci 19:1599–1609PubMedGoogle Scholar
  69. 69.
    Koob GF (2006) The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction 101(Suppl 1):23–30PubMedGoogle Scholar
  70. 70.
    Kreitzer AC, Malenka RC (2005) Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci 25:10537–10545PubMedGoogle Scholar
  71. 71.
    Lee HK, Min SS, Gallagher M, Kirkwood A (2005) NMDA receptor-independent long-term depression correlates with successful aging in rats. Nat Neurosci 8:1657–1659PubMedGoogle Scholar
  72. 72.
    Lee O, Lee CJ, Choi S (2002) Induction mechanisms for L-LTP at thalamic input synapses to the lateral amygdala: requirement of mGluR5 activation. Neuroreport 13:685–691PubMedGoogle Scholar
  73. 73.
    Leri F, Flores J, Rodaros D, Stewart J (2002) Blockade of stress-induced but not cocaine-induced reinstatement by infusion of noradrenergic antagonists into the bed nucleus of the stria terminalis or the central nucleus of the amygdala. J Neurosci 22:5713–5718PubMedGoogle Scholar
  74. 74.
    Linden DJ, Dickinson MH, Smeyne M, Connor JA (1991) A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron 7:81–89PubMedGoogle Scholar
  75. 75.
    Liu QS, Pu L, Poo MM (2005) Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature 437:1027–1031PubMedGoogle Scholar
  76. 76.
    Lominac KD, Kapasova Z, Hannun RA, Patterson C, Middaugh LD, Szumlinski KK (2006) Behavioral and neurochemical interactions between group 1 mGluR antagonists and ethanol: Potential insight into their anti-addictive properties. Drug Alcohol Depend 85:142–156PubMedGoogle Scholar
  77. 77.
    Lopez-Bendito G, Shigemoto R, Fairen A, Lujan R (2002) Differential distribution of group I metabotropic glutamate receptors during rat cortical development. Cereb Cortex 12:625–638PubMedGoogle Scholar
  78. 78.
    Lujan R, Roberts JD, Shigemoto R, Ohishi H, Somogyi P (1997) Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat 13:219–241PubMedGoogle Scholar
  79. 79.
    Manzoni O, Michel JM, Bockaert J (1997) Metabotropic glutamate receptors in the rat nucleus accumbens. Eur J Neurosci 9:1514–1523PubMedGoogle Scholar
  80. 80.
    Mao L, Yang L, Arora A, Choe ES, Zhang G, Liu Z, Fibuch EE, Wang JQ (2005) Role of protein phosphatase 2 A in mGluR5-regulated MEK/ERK phosphorylation in neurons. J Biol Chem 280:12602–12610PubMedGoogle Scholar
  81. 81.
    Massey PV, Bhabra G, Cho K, Brown MW, Bashir ZI (2001) Activation of muscarinic receptors induces protein synthesis-dependent long-lasting depression in the perirhinal cortex. Eur J Neurosci 14:145–152PubMedGoogle Scholar
  82. 82.
    Mato S, Robbe D, Puente N, Grandes P, Manzoni OJ (2005) Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure. J Neurosci 25:11619–11627PubMedGoogle Scholar
  83. 83.
    Mato S, Chevaleyre V, Robbe D, Pazos A, Castillo PE, Manzoni OJ (2004) A single in-vivo exposure to delta 9THC blocks endocannabinoid-mediated synaptic plasticity. Nat Neurosci 7:585–586PubMedGoogle Scholar
  84. 84.
    Mazzucchelli C, Brambilla R (2000) Ras-related and MAPK signalling in neuronal plasticity and memory formation. Cell Mol Life Sci 57:604–611PubMedGoogle Scholar
  85. 85.
    Moult PR, Schnabel R, Kilpatrick IC, Bashir ZI, Collingridge GL (2002) Tyrosine dephosphorylation underlies DHPG-induced LTD. Neuropharmacology 43:175–180PubMedGoogle Scholar
  86. 86.
    Moult PR, Gladding CM, Sanderson TM, Fitzjohn SM, Bashir ZI, Molnar E, Collingridge GL (2006) Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. J Neurosci 26:2544–2554PubMedGoogle Scholar
  87. 87.
    Nosyreva ED, Huber KM (2005) Developmental switch in synaptic mechanisms of hippocampal metabotropic glutamate receptor-dependent long-term depression. J Neurosci 25:2992–3001PubMedGoogle Scholar
  88. 88.
    Nosyreva ED, Huber KM (2006) Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. J Neurophysiol 95:3291–3295PubMedGoogle Scholar
  89. 89.
    Oh MC, Derkach VA, Guire ES, Soderling TR (2006) Extrasynaptic membrane trafficking regulated by GluR1 serine 845 phosphorylation primes AMPA receptors for long-term potentiation. J Biol Chem 281:752–758PubMedGoogle Scholar
  90. 90.
    Oliet SH, Malenka RC, Nicoll RA (1997) Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron 18:969–982PubMedGoogle Scholar
  91. 91.
    Orban PC, Chapman PF, Brambilla R (1999) Is the Ras-MAPK signalling pathway necessary for long-term memory formation? Trends Neurosci 22:38–44PubMedGoogle Scholar
  92. 92.
    Otani S, Connor JA (1998) Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus. J Physiol 511(Pt 3):761–770PubMedGoogle Scholar
  93. 93.
    Palmer MJ, Irving AJ, Seabrook GR, Jane DE, Collingridge GL (1997) The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus. Neuropharmacology 36:1517–1532PubMedGoogle Scholar
  94. 94.
    Pin JP, Kniazeff J, Goudet C, Bessis AS, Liu J, Galvez T, Acher F, Rondard P, Prezeau L (2004) The activation mechanism of class-C G-protein coupled receptors. Biol Cell 96:335–342PubMedGoogle Scholar
  95. 95.
    Poisik OV, Mannaioni G, Traynelis S, Smith Y, Conn PJ (2003) Distinct functional roles of the metabotropic glutamate receptors 1 and 5 in the rat globus pallidus. J Neurosci 23:122–130PubMedGoogle Scholar
  96. 96.
    Ritzen A, Mathiesen JM, Thomsen C (2005) Molecular pharmacology and therapeutic prospects of metabotropic glutamate receptor allosteric modulators. Basic Clin Pharmacol Toxicol 97:202–213PubMedGoogle Scholar
  97. 97.
    Robbe D, Alonso G, Chaumont S, Bockaert J, Manzoni OJ (2002a) Role of p/q-Ca2+ channels in metabotropic glutamate receptor 2/3-dependent presynaptic long-term depression at nucleus accumbens synapses. J Neurosci 22:4346–4356PubMedGoogle Scholar
  98. 98.
    Robbe D, Kopf M, Remaury A, Bockaert J, Manzoni OJ (2002b) Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proc Natl Acad Sci USA 99:8384–8388PubMedGoogle Scholar
  99. 99.
    Romano C, Sesma MA, McDonald CT, O’Malley K, Van den Pol AN, Olney JW (1995) Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol 355:455–469PubMedGoogle Scholar
  100. 100.
    Rouach N, Nicoll RA (2003) Endocannabinoids contribute to short-term but not long-term mGluR-induced depression in the hippocampus. Eur J Neurosci 18:1017–1020PubMedGoogle Scholar
  101. 101.
    Rush AM, Wu J, Rowan MJ, Anwyl R (2002) Group I metabotropic glutamate receptor (mGluR)-dependent long-term depression mediated via p38 mitogen-activated protein kinase is inhibited by previous high-frequency stimulation and activation of mGluRs and protein kinase C in the rat dentate gyrus in vitro. J Neurosci 22:6121–6128PubMedGoogle Scholar
  102. 102.
    Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582PubMedGoogle Scholar
  103. 103.
    Scheiderer CL, Dobrunz LE, McMahon LL (2004) Novel form of long-term synaptic depression in rat hippocampus induced by activation of alpha 1 adrenergic receptors. J Neurophysiol 91:1071–1077PubMedGoogle Scholar
  104. 104.
    Scheiderer CL, McCutchen E, Thacker EE, Kolasa K, Ward MK, Parsons D, Harrell LE, Dobrunz LE, McMahon LL (2006) Sympathetic sprouting drives hippocampal cholinergic reinnervation that prevents loss of a muscarinic receptor-dependent long-term depression at CA3-CA1 synapses. J Neurosci 26:3745–3756PubMedGoogle Scholar
  105. 105.
    Schlicker E, Kathmann M (2001) Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol Sci 22:565–572PubMedGoogle Scholar
  106. 106.
    Schramm-Sapyta NL, Olsen CM, Winder DG (2006) Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell. Neuropsychopharmacology 31:1444–1451PubMedGoogle Scholar
  107. 107.
    Shigemoto R, Abe T, Nomura S, Nakanishi S, Hirano T (1994) Antibodies inactivating mGluR1 metabotropic glutamate receptor block long-term depression in cultured Purkinje cells. Neuron 12:1245–1255PubMedGoogle Scholar
  108. 108.
    Shigemoto R, Nomura S, Ohishi H, Sugihara H, Nakanishi S, Mizuno N (1993) Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain. Neurosci Lett 163:53–57PubMedGoogle Scholar
  109. 109.
    Snyder EM, Philpot BD, Huber KM, Dong X, Fallon JR, Bear MF (2001) Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat Neurosci 4:1079–1085PubMedGoogle Scholar
  110. 110.
    Steinberg JP, Takamiya K, Shen Y, Xia J, Rubio ME, Yu S, Jin W, Thomas GM, Linden DJ, Huganir RL (2006) Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 49:845–860PubMedGoogle Scholar
  111. 111.
    Sung KW, Choi S, Lovinger DM (2001) Activation of group I mGluRs is necessary for induction of long-term depression at striatal synapses. J Neurophysiol 86:2405–2412PubMedGoogle Scholar
  112. 112.
    Swanson CJ, Baker DA, Carson D, Worley PF, Kalivas PW (2001) Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer. J Neurosci 21:9043–9052PubMedGoogle Scholar
  113. 113.
    Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD (2005) Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 4:131–144PubMedGoogle Scholar
  114. 114.
    Sweatt JD (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10PubMedGoogle Scholar
  115. 115.
    Szumlinski KK, Kalivas PW, Worley PF (2006) Homer proteins: implications for neuropsychiatric disorders. Curr Opin Neurobiol 16:251–257PubMedGoogle Scholar
  116. 116.
    Szumlinski KK, Lominac KD, Oleson EB, Walker JK, Mason A, Dehoff MH, Klugmann M, Cagle S, Welt K, During M, Worley PF, Middaugh LD, Kalivas PW (2005) Homer2 is necessary for EtOH-induced neuroplasticity. J Neurosci 25:7054–7061PubMedGoogle Scholar
  117. 117.
    Szumlinski KK, Dehoff MH, Kang SH, Frys KA, Lominac KD, Klugmann M, Rohrer J, Griffin W, 3rd, Toda S, Champtiaux NP, Berry T, Tu JC, Shealy SE, During MJ, Middaugh LD, Worley PF, Kalivas PW (2004) Homer proteins regulate sensitivity to cocaine. Neuron 43:401–413PubMedGoogle Scholar
  118. 118.
    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 4:1217–1223PubMedGoogle Scholar
  119. 119.
    Thompson AM, Swant J, Gosnell BA, Wagner JJ (2004) Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration. Neuroscience 127:177–185PubMedGoogle Scholar
  120. 120.
    Todd PK, Mack KJ, Malter JS (2003) The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95. Proc Natl Acad Sci USA 100:14374–14378PubMedGoogle Scholar
  121. 121.
    Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PF (1999) Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23:583–592PubMedGoogle Scholar
  122. 122.
    Ungless MA, Whistler JL, Malenka RC, Bonci A (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411:583–587PubMedGoogle Scholar
  123. 123.
    Valjent E, Pages C, Herve D, Girault JA, Caboche J (2004) Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. Eur J Neurosci 19:1826–1836PubMedGoogle Scholar
  124. 124.
    Volk LJ, Daly CA, Huber KM (2006) Differential roles for group 1 mGluR subtypes in induction and expression of chemically induced hippocampal long-term depression. J Neurophysiol 95:2427–2438PubMedGoogle Scholar
  125. 125.
    Wang YT, Linden DJ (2000) Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25:635–647PubMedGoogle Scholar
  126. 126.
    Watabe AM, Carlisle HJ, O’Dell TJ (2002) Postsynaptic induction and presynaptic expression of group 1 mGluR-dependent LTD in the hippocampal CA1 region. J Neurophysiol 87:1395–1403PubMedGoogle Scholar
  127. 127.
    Winder DG, Sweatt JD (2001) Roles of serine/threonine phosphatases in hippocampal synaptic plasticity. Nat Rev Neurosci 2:461–474PubMedGoogle Scholar
  128. 128.
    Winder DG, Egli RE, Schramm NL, Matthews RT (2002) Synaptic plasticity in drug reward circuitry. Curr Mol Med 2:667–676PubMedGoogle Scholar
  129. 129.
    Wolf ME, Sun X, Mangiavacchi S, Chao SZ (2004) Psychomotor stimulants and neuronal plasticity. Neuropharmacology 47(Suppl 1):61–79PubMedGoogle Scholar
  130. 130.
    Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ (2000) Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron 28:499–510PubMedGoogle Scholar
  131. 131.
    Xiao MY, Zhou Q, Nicoll RA (2001) Metabotropic glutamate receptor activation causes a rapid redistribution of AMPA receptors. Neuropharmacology 41:664–671PubMedGoogle Scholar
  132. 132.
    Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Cyr M, Beaulieu JM, Torres GE, Grant SG, Caron MG (2004) Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 41:625–638PubMedGoogle Scholar
  133. 133.
    Zakharenko SS, Zablow L, Siegelbaum SA (2002) Altered presynaptic vesicle release and cycling during mGluR-dependent LTD. Neuron 35:1099–1110PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Brad A. Grueter
    • 1
  • Zoé A. McElligott
    • 2
  • Danny G. Winder
    • 1
    • 2
    • 3
  1. 1.Department of Molecular Physiology and BiophysicsVanderbilt University School of MedicineNashvilleUSA
  2. 2.Neuroscience Graduate ProgramVanderbilt University School of MedicineNashvilleUSA
  3. 3.Vanderbilt Brain InstituteVanderbilt University School of MedicineNashvilleUSA

Personalised recommendations