Molecular Neurobiology

, Volume 25, Issue 2, pp 191–212 | Cite as

Glutamate receptor genes

Susceptibility factors in schizophrenia and depressive disorders?
Article

Abstract

Schizophrenia, depression, and bipolar disorder are three major neuropsychiatric disorders that are among the leading causes of disability and have enormous economic impacts on our society. Although several neurotransmitter systems have been suggested to play a role in their etiology, we still have not identified any gene or molecular mechanism that might lead to genetic susceptibility for or protection against these neuropsychiatric disorders. The glutamatergic receptor system, and in particular the N-methyl-D-aspartate (NMDA) receptor complex, has long been implicated in their etiology. I review the current molecular evidence that supports a critical role for the glutamatergic receptor system in schizophrenia and the potential involvement of this receptor system in depression and bipolar disorder. It is likely that mutations in glutamate receptor genes might alter the risk of developing one of these disorders. Potential future research directions designed to identify these mutations and to elucidate their effect on mental health will be discussed.

Index Entries

Glutamate receptor schizophrenia bipolar disorder major depression NMDA AMPA kainate ionotropic metabotropic genetic susceptibility dopamine glutamate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cooper B. (2001) Nature, nurture and mental disorder: old concepts in the new millennium. Br. J. Psychiatry Suppl. 40, S91–101.PubMedGoogle Scholar
  2. 2.
    Manji H. K., Drevets W. C., and Charney D. S. (2001) The cellular neurobiology of depression. Nat. Med. 7, 541–547.PubMedGoogle Scholar
  3. 3.
    Lewis D. A. and Lieberman J. A. (2000) Catching up on schizophrenia: natural history and neurobiology. Neuron 28, 325–334.PubMedGoogle Scholar
  4. 4.
    Olney J. W., Newcomer J. W., and Farber N. B. (1999) NMDA receptor hypofunction model of schizophrenia. J. Psychiatr. Res. 33, 523–533.PubMedGoogle Scholar
  5. 5.
    Carlsson A., Waters N., Holm-Waters S., Tedroff J., Nilsson M., and Carlsson M. L. (2001) Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu. Rev. Pharmacol. Toxicol. 41, 237–260.PubMedGoogle Scholar
  6. 6.
    Hollmann M. and Heinemann S. (1994) Cloned glutamate receptors. Annu. Rev. Neurosci. 17, 31–108.PubMedGoogle Scholar
  7. 7.
    Nakanishi S., Nakajima Y., Masu M., Ueda Y., Nakahara K., Watanabe D., et al. (1998) Glutamate receptors: brain function and signal transduction. Brain Res. Brain Res. Rev. 26, 230–235.PubMedGoogle Scholar
  8. 8.
    Dingledine R., Borges K., Bowie D., and Traynelis S. F. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61.PubMedGoogle Scholar
  9. 9.
    Lerma J., Paternain A. V., Rodriguez-Moreno A., and Lopez-Garcia J. C. (2001) Molecular physiology of kainate receptors. Physiol. Rev. 81, 971–998.PubMedGoogle Scholar
  10. 10.
    Skerry T. M. and Genever P. G. (2001) Glutamate signalling in non-neuronal tissues. Trends Pharmacol. Sci. 22, 174–181.PubMedGoogle Scholar
  11. 11.
    Scannevin R. H. and Huganir R. L. (2000) Postsynaptic organization and regulation of excitatory synapses. Nat. Rev. Neurosci. 1, 133–141.PubMedGoogle Scholar
  12. 12.
    Hollmann M., Maron C., and Heinemann S. (1994) N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13, 1331–1343.PubMedGoogle Scholar
  13. 13.
    VanDongen H. M. and VanDongen A. M. (1999) Determination of membrane topology of glutamate receptors. Methods Mol. Biol. 128, 155–166.PubMedGoogle Scholar
  14. 14.
    Verdoorn T. A., Burnashev N., Monyer H., Seeburg P. H., and Sakmann B. (1991) Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252, 1715–1718.PubMedGoogle Scholar
  15. 15.
    Hume R. I., Dingledine R., and Heinemann S. F. (1991) Identification of a site in glutamate receptor subunits that controls calcium permeability. Science 253, 1028–1031.PubMedGoogle Scholar
  16. 16.
    Stern-Bach Y., Bettler B., Hartley M., Sheppard P. O., O’Hara P. J., and Heinemann S. F. (1994) Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13, 1345–1357.PubMedGoogle Scholar
  17. 17.
    Ferrer-Montiel A. V. and Montal M. (1996) Pentameric subunit stoichiometry of a neuronal glutamate receptor. Proc. Natl. Acad. Sci. USA 93, 2741–2744.PubMedGoogle Scholar
  18. 18.
    Rosenmund C., Stern-Bach Y., and Stevens C. F. (1998) The tetrameric structure of a glutamate receptor channel. Science 280, 1596–1599.PubMedGoogle Scholar
  19. 19.
    Kennedy M. B. (1997) The postsynaptic density at glutamatergic synapses. Trends Neurosci. 20, 264–268.PubMedGoogle Scholar
  20. 20.
    Sheng M. (2001) Molecular organization of the postsynaptic specialization. Proc. Natl. Acad. Sci. USA 98, 7058–7061.PubMedGoogle Scholar
  21. 21.
    Tomita S., Nicoll R. A., and Bredt D. S. (2001) PDZ protein interactions regulating glutamate receptor function and plasticity. J. Cell Biol. 153, F19–24.PubMedGoogle Scholar
  22. 22.
    Sattler R. and Tymianski M. (2000) Molecular mechanisms of calcium-dependent excitotoxicity. J. Mol. Med. 78, 3–13.PubMedGoogle Scholar
  23. 23.
    McNamara J. O. (1993) Excitatory amino acid receptors and epilepsy. Curr. Opin. Neurol. Neurosurg. 6, 583–587.PubMedGoogle Scholar
  24. 24.
    Lee J. M., Zipfel G. J., and Choi D. W. (1999) The changing landscape of ischaemic brain injury mechanisms. Nature 399, A7–14.PubMedGoogle Scholar
  25. 25.
    Weiss J. H. and Sensi S. L. (2000) Ca2+-Zn2+permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci. 23, 365–371.PubMedGoogle Scholar
  26. 26.
    Zipfel G. J., Babcock D. J., Lee J. M., and Choi D. W. (2000) Neuronal apoptosis after CNS injury: the roles of glutamate and calcium. J. Neurotrauma 17, 857–869.PubMedGoogle Scholar
  27. 27.
    Seeburg P. H. (1996) The role of RNA editing in controlling glutamate receptor channel properties. J. Neurochem. 66, 1–5.PubMedGoogle Scholar
  28. 28.
    Maas S., Melcher T., and Seeburg P. H. (1997) Mammalian RNA-dependent deaminases and edited mRNAs. Curr. Opin. Cell Biol. 9, 343–349.PubMedGoogle Scholar
  29. 29.
    Higuchi M., Single F. N., Kohler M., Sommer B., Sprengel R., and Seeburg P. H. (1993) RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell 75, 1361–1370.PubMedGoogle Scholar
  30. 30.
    Sommer B., Kohler M., Sprengel R., and Seeburg P. H. (1991) RNA editing in brain controls a determinant of ion flow in glutamate- gated channels. Cell 67, 11–19.PubMedGoogle Scholar
  31. 31.
    Pellicciari R., Costantino G., and Macchiarulo A. (2000) Metabotropic glutamate receptors: a structural view point. Pharm. Acta. Helv. 74, 231–237.PubMedGoogle Scholar
  32. 32.
    Alagarsamy S., Sorensen S. D., and Conn P. J. (2001) Coordinate regulation of metabotropic glutamate receptors. Curr. Opin. Neurobiol. 11, 357–362.PubMedGoogle Scholar
  33. 33.
    Spooren W. P. J. M., Gasparini F., Salt T. E., and Kuhn R. (2001) Novel allosteric antagonists shed light on mGluR5 receptors and CNS disorders. Trends Pharmacol. Sci. 22, 331–337.PubMedGoogle Scholar
  34. 34.
    Seal R. P. and Amara S. G. (1999) Excitatory amino acid transporters: a family in flux. Annu. Rev. Pharmacol. Toxicol. 39, 431–456.PubMedGoogle Scholar
  35. 35.
    DeFelice L. J. and Blakely R. D. (1996) Pore models for transporters? Biophys. J. 70, 579–580.PubMedGoogle Scholar
  36. 36.
    Gaal L., Roska B., Picaud S. A., Wu S. M., Marc R., and Werblin F. S. (1998) Postsynaptic response kinetics are controlled by a glutamate transporter at cone photoreceptors. J. Neurophysiol. 79, 190–196.PubMedGoogle Scholar
  37. 37.
    Masliah E., Alford M., DeTeresa R., Mallory M., and Hansen L. (1996) Deficient glutamate transport is associated with neurodegeneration in Alzheimer’s disease. Ann. Neurol. 40, 759–766.PubMedGoogle Scholar
  38. 38.
    Shaw P. J. (1999) Calcium, glutamate, and amyotrophic lateral sclerosis: more evidence but no certainties. Ann. Neurol. 46, 803–805.PubMedGoogle Scholar
  39. 39.
    Kim J. S., Kornhuber H. H., Schmid-Burgk W., and Holzmuller B. (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci. Lett. 20, 379–382.PubMedGoogle Scholar
  40. 40.
    Sharp F. R., Tomitaka M., Bernaudin M., and Tomitaka S. (2001) Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends Neurosci. 24, 330–334.PubMedGoogle Scholar
  41. 41.
    Krystal J. H., D’Souza D. C., Petrakis I. L., Belger A., Berman R. M., Charney D. S., et al. (1999) NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv. Rev. Psychiatry 7, 125–143.PubMedGoogle Scholar
  42. 42.
    Krystal J. H., Karper L. P., Seibyl J. P., Freeman G. K., Delaney R., Bremner J. D., et al. (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch. Gen. Psychiatry 51, 199–214.PubMedGoogle Scholar
  43. 43.
    Corssen G. and Domino E. F. (1966) Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth. Analg. 45, 29–40.PubMedGoogle Scholar
  44. 44.
    Domino E. F., Chodoff P., and Corssen G. (1965) Pharmacological effects of CI-581, a new dissociative anesthetic in man. Clin. Pharmacol. Ther. 6, 279–291.PubMedGoogle Scholar
  45. 45.
    Cohen B. D., Rosenbaum G., Luby E. D., and Gottlieb J. S. (1962) Comparison of phencyclidine hydrochloride (sernyl) with other drugs: simulation of schizophrenic performance with phencyclidine hydrochloride (sernyl)lysergic acid diethylamide (LSD-25), and amobarbital (Amytal)sodium: II. Symbolic and sequential thinking. Arch. Gen. Psychiatry 6, 79–85.Google Scholar
  46. 46.
    Bakker C. B. and Amini F. B. (1961) Observations on the psychomimetic effects of sernyl. Compr. Psychiatry 2, 269–280.PubMedGoogle Scholar
  47. 47.
    Davies B. M. and Beech H. R. (1960) The effect of 1-arylcyclohexylamine (sernyl) on twelve normal volunteers. J. Ment. Sci. 106, 912–924.PubMedGoogle Scholar
  48. 48.
    Luby E. D., Cohen B. D., Rosenbaum G., Gottlieb J. S., and Kelley R. (1959) Study of a new schizophrenomimetic drug: Sernyl. Arch. Neurol. Psychiatry 81, 363–369.Google Scholar
  49. 49.
    Malhotra A. K., Pinals D. A., Adler C. M., Elman I., Clifton A., Pickar D., and Breier A. (1997) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17, 141–150.PubMedGoogle Scholar
  50. 50.
    Javitt D. C. and Zukin S. R. (1991) Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry, 148, 1301–1308.PubMedGoogle Scholar
  51. 51.
    Cull-Candy S., Brickley S., and Farrant M. (2001) NMDA receptor subunits: diversity, development and disease. Curr. Opin. Neurobiol. 11, 327–335.PubMedGoogle Scholar
  52. 52.
    Brauner-Osborne H., Egebjerg J., Nielsen E. O., Madsen U., and Krogsgaard-Larsen P. (2000) Ligands for glutamate receptors: design and therapeutic prospects. J. Med. Chem. 43, 2609–2645.PubMedGoogle Scholar
  53. 53.
    Noda A., Noda Y., Kamei H., Ichihara K., Mamiya T., Nagai T., et al. (2001) Phencyclidine impairs latent learning in mice: interaction between glutamatergic systems and sigma(1) receptors. Neuropsychopharmacology 24, 451–460.PubMedGoogle Scholar
  54. 54.
    Miyamoto Y., Yamada K., Noda Y., Mori H., Mishina M., and Nabeshima T. (2001) Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking the NMDA receptor epsilon1 subunit. J. Neurosci. 21, 750–757.PubMedGoogle Scholar
  55. 55.
    Mohn A. R., Gainetdinov R. R., Caron M. G., and Koller B. H. (1999) Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98, 427–436.PubMedGoogle Scholar
  56. 56.
    Sams-Dodd F. F. (1996) Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia. Behav. Pharmacol. 7, 3–23.PubMedGoogle Scholar
  57. 57.
    Handelmann G. E., Contreras P. C., and O’Donohue T. L. (1987) Selective memory impairment by phencyclidine in rats. Eur. J. Pharmacol. 140, 69–73.PubMedGoogle Scholar
  58. 58.
    Sturgeon R. D., Fessler R. G., and Meltzer H. Y. (1979) Behavioral rating scales for assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats. Eur. J. Pharmacol. 59, 169–179.PubMedGoogle Scholar
  59. 59.
    Schlemmer R. F., Jr., Jackson J. A., Preston K. L., Bederka J. P., Jr., Garver D. L., and Davis J. M. (1978) Phencyclidine-induced stereotyped behavior in monkeys: antagonism by pimozide. Eur. J. Pharmacol. 52, 379–384.PubMedGoogle Scholar
  60. 60.
    Moghaddam B. and Adams B. W. (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281, 1349–1352.PubMedGoogle Scholar
  61. 61.
    Corbett R., Camacho F., Woods A. T., Kerman L. L., Fishkin R. J., Brooks K., and Dunn R. W. (1995) Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviors. Psychopharmacology (Berl) 120, 67–74.Google Scholar
  62. 62.
    Carlsson M. and Carlsson A. (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia—implications for schizophrenia and Parkinson’s disease. Trends Neurosci. 13, 272–276.PubMedGoogle Scholar
  63. 63.
    Moghaddam B., Adams B., Verma A., and Daly D. (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J. Neurosci. 17, 2921–2927.PubMedGoogle Scholar
  64. 64.
    Willins D. L., Narayanan S., Wallace L. J., and Uretsky N. J. (1993) The role of dopamine and AMPA/kainate receptors in the nucleus accumbens in the hypermotility response to MK801. Pharmacol. Biochem. Behav. 46, 881–887.PubMedGoogle Scholar
  65. 65.
    Angrist B. M. and Gershon S. (1970) The phenomenology of experimentally induced amphetamine psychosis: preliminary observations. Biol. Psychiatry 2, 95–107.PubMedGoogle Scholar
  66. 66.
    Bell D. (1965) Comparison of amphetamine psychosis and schizophrenia. Am. J. Psychiatry 111, 701–707.Google Scholar
  67. 67.
    White F. J. and Kalivas P. W. (1998) Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend. 51, 141–153.PubMedGoogle Scholar
  68. 68.
    Giros B., Jaber M., Jones S. R., Wightman R. M., and Caron M. G. (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379, 606–612.PubMedGoogle Scholar
  69. 69.
    Heikkila R. E., Orlansky H., and Cohen G. (1975) Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices. Biochem. Pharmacol. 24, 847–852.PubMedGoogle Scholar
  70. 70.
    Zhuang X., Oosting R. S., Jones S. R., Gainetdinov R. R., Miller G. W., Caron M. G., and Hen R. (2001) Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc. Natl. Acad. Sci. USA 98, 1982–1987.PubMedGoogle Scholar
  71. 71.
    Uhl G. R., Vandenbergh D. J., and Miner L. L. (1996) Knockout mice and dirty drugs. Drug addiction. Curr. Biol. 6, 935–936.PubMedGoogle Scholar
  72. 72.
    Creese I. and Iversen S. D. (1973) Blockage of amphetamine induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res. 55, 369–382.PubMedGoogle Scholar
  73. 73.
    Creese I. and Iversen S. D. (1972) Amphetamine response in rat after dopamine neurone destruction. Nat. New Biol. 238, 247–248.PubMedGoogle Scholar
  74. 74.
    Laruelle M., Abi-Dargham A., Gil R., Kegeles L., and Innis R. (1999) Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol. Psychiatry 46, 56–72.PubMedGoogle Scholar
  75. 75.
    Abi-Dargham A., Gil R., Krystal J., Baldwin R. M., Seibyl J. P., Bowers M., et al. (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am. J. Psychiatry 155, 761–767.PubMedGoogle Scholar
  76. 76.
    Breier A., Su T. P., Saunders R., Carson R. E., Kolachana B. S., de Bartolomeis A., et al. (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc. Natl. Acad. Sci. USA 94, 2569–2574.PubMedGoogle Scholar
  77. 77.
    Duncan G. E., Sheitman B. B., and Lieberman J. A. (1999) An integrated view of pathophysiological models of schizophrenia. Brain Res. Brain Res. Rev. 29, 250–264.PubMedGoogle Scholar
  78. 78.
    Creese I., Burt D. R., and Synder S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192, 481–483.PubMedGoogle Scholar
  79. 79.
    Rowley M., Bristow L. J., and Hutson P. H. (2001) Current and novel approaches to the drug treatment of schizophrenia. J. Med. Chem. 44, 477–501.PubMedGoogle Scholar
  80. 80.
    Jackson D. M., Johansson C., Lindgren L. M., and Bengtsson A. (1994) Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats. Pharmacol. Biochem. Behav. 48, 465–471.PubMedGoogle Scholar
  81. 81.
    Ogren S. O. and Goldstein M. (1994) Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated. Neuropsychopharmacology 11, 167–177.PubMedGoogle Scholar
  82. 82.
    Castellani S. and Adams P. M. (1981) Effects of dopaminergic drugs on phencyclidine-induced behavior in the rat. Neuropharmacology 20, 371–374.PubMedGoogle Scholar
  83. 83.
    Farber N. B., Foster J., Duhan N. L., and Olney J. W. (1996) Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity. Schizophr. Res. 21, 33–37.PubMedGoogle Scholar
  84. 84.
    Walaas S. I. and Greengard P. (1984) DARPP-32, a dopamine- and adenosine 3′:5′-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. I. Regional and cellular distribution in the rat brain. J. Neurosci. 4, 84–98.PubMedGoogle Scholar
  85. 85.
    Langley K. C., Bergson C., Greengard P., and Ouimet C. C. (1997) Co-localization of the D1 dopamine receptor in a subset of DARPP-32-containing neurons in rat caudate-putamen. Neuroscience 78, 977–983.PubMedGoogle Scholar
  86. 86.
    Ouimet C. C., Langley-Gullion K. C., and Greengard P. (1998) Quantitative immunocytochemistry of DARPP-32-expressing neurons in the rat caudatoputamen. Brain Res. 808, 8–12.PubMedGoogle Scholar
  87. 87.
    Snyder G. L., Allen P. B., Fienberg A. A., Valle C. G., Huganir R. L., Nairn A. C., and Greengard P. (2000) Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. J. Neurosci. 20, 4480–4488.PubMedGoogle Scholar
  88. 88.
    Snyder G. L., Fienberg A. A., Huganir R. L., and Greengard P. (1998) A dopamine/D1 receptor/protein kinase A/dopamine- and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor. J. Neurosci. 18, 10297–10303.PubMedGoogle Scholar
  89. 89.
    Fienberg A. A. and Greengard P. (2000) The DARPP-32 knockout mouse. Brain Res. Brain Res. Rev. 31, 313–319.PubMedGoogle Scholar
  90. 90.
    Larson J., Quach C. N., LeDuc B. Q., Nguyen A., Rogers G. A., and Lynch G. (1996) Effects of an AMPA receptor modulator on methamphetamine-induced hyperactivity in rats. Brain Res. 738, 353–356.PubMedGoogle Scholar
  91. 91.
    Johnson S. A., Luu N. T., Herbst T. A., Knapp R., Lutz D., Arai A., et al. (1999) Synergistic interactions between ampakines and antipsychotic drugs. J. Pharmacol. Exp. Ther. 289, 392–397.PubMedGoogle Scholar
  92. 92.
    Farber N. B., Newcomer J. W., and Olney J. W. (1999) Glycine agonists: what can they teach us about schizophrenia? Arch. Gen. Psychiatry 56, 13–17.PubMedGoogle Scholar
  93. 93.
    Goff D. C., Tsai G., Manoach D. S., and Coyle J. T. (1995) Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia. Am. J. Psychiatry 152, 1213–1215.PubMedGoogle Scholar
  94. 94.
    van Berckel B. N., Hijman R., van der Linden J. A., Westenberg H. G., van Ree J. M., and Kahn R. S. (1996) Efficacy and tolerance of D-cycloserine in drug-free schizophrenic patients. Biol. Psychiatry 40, 1298–1300.PubMedGoogle Scholar
  95. 95.
    Goff D. C., Tsai G., Manoach D. S., Flood J., Darby D. G., and Coyle J. T. (1996) D-cycloserine added to clozapine for patients with schizophrenia. Am. J. Psychiatry 153, 1628–1630.PubMedGoogle Scholar
  96. 96.
    Goff D. C., Tsai G., Levitt J., Amico E., Manoach D., Schoenfeld D. A., et al. (1999) A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch. Gen. Psychiatry 56, 21–27.PubMedGoogle Scholar
  97. 97.
    van Berckel B. N., Evenblij C. N., van Loon B. J., Maas M. F., van der Geld M. A., Wynne H. J., et al. (1999) D-cycloserine increases positive symptoms in chronic schizophrenic patients when administered in addition to antipsychotics: a double- blind, parallel, placebo-controlled study. Neuropsychopharmacology 21, 203–210.PubMedGoogle Scholar
  98. 98.
    Petrie R. X., Reid I. C., and Stewart C. A. (2000) The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder. A critical review. Pharmacol. Ther. 87, 11–25.PubMedGoogle Scholar
  99. 99.
    Sernagor E., Kuhn D., Vyklicky L., Jr., and Mayer M. L. (1989) Open channel block of NMDA receptor responses evoked by tricyclic antidepressants. Neuron 2, 1221–1227.PubMedGoogle Scholar
  100. 100.
    Kitamura Y., Zhao X. H., Tekei M., Yonemitsu O., and Nomura Y. (1991) Effects of antidepressants on the glutamatergic system in the mouse brain. Neurochem. Int. 19, 247–253.Google Scholar
  101. 101.
    Lucki I. (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav. Pharmacol. 8, 523–532.PubMedGoogle Scholar
  102. 102.
    Steru L., Chermat R., Thierry B., and Simon P. (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85, 367–370.PubMedGoogle Scholar
  103. 103.
    Maier S. F. (1984) Learned helplessness and animal models of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 8, 435–446.PubMedGoogle Scholar
  104. 104.
    Willner P. (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 134, 319–329.Google Scholar
  105. 105.
    Berman R. M., Cappiello A., Anand A., Oren D. A., Heninger G. R., Charney D. S., and Krystal J. H. (2000) Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 47, 351–354.PubMedGoogle Scholar
  106. 106.
    Paladini C. A., Fiorillo C. D., Morikawa H., and Williams J. T. (2001) Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. Nat. Neurosci. 4, 275–281.PubMedGoogle Scholar
  107. 107.
    Linden A., Yu H., Zarrinmay eh H., Wheeler W. J., and Skolnick P. (2001) Binding of an AMPA receptor potentiator. Neuropharmacology 40, 1010–1018.PubMedGoogle Scholar
  108. 108.
    Legutko B., Li X., and Skolnick P. (2001) Regulation of BDNF expression in primary neuron culture by LY392098, a novel AMPA receptor potentiator. Neuropharmacology 40, 1019–1027.PubMedGoogle Scholar
  109. 109.
    Siuciak J. A., Lewis D. R., Wiegand S. J., and Lindsay R. M. (1997) Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol. Biochem. Behav. 56, 131–137.PubMedGoogle Scholar
  110. 110.
    Altar C. A. (1999) Neurotrophins and depression. Trends Pharmacol. Sci. 20, 59–61.PubMedGoogle Scholar
  111. 111.
    Tatarczynska E., Klodzinska A., Chojnacka-Wojcik E., Palucha A., Gasparini F., Kuhn R., and Pilc A. (2001) Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br. J. Pharmacol. 132, 1423–1430.PubMedGoogle Scholar
  112. 112.
    Gasparini F., Lingenhohl K., Stoehr N., Flor P. J., Heinrich M., Vranesic I., et al. (1999) 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38, 1493–1503.PubMedGoogle Scholar
  113. 113.
    Soares J. C. and Gershon S. (1998) The lithium ion: a foundation for psychopharmacological specificity. Neuropsychopharmacology 19, 167–182.PubMedGoogle Scholar
  114. 114.
    Karkanias N. B. and Papke R. L. (1999) Lithium modulates desensitization of the glutamate receptor subtype gluR3 in Xenopus occytes. Neurosci. Lett. 277, 153–156.PubMedGoogle Scholar
  115. 115.
    Karkanias N. B. and Papke R. L. (1999) Subtype-specific effects of lithium on glutamate receptor function. J. Neurophysiol. 81, 1506–1512.PubMedGoogle Scholar
  116. 116.
    Phiel C. J. and Klein P. S. (2001) Molecular targets of lithium action. Annu. Rev. Pharmacol. Toxicol. 41, 789–813.PubMedGoogle Scholar
  117. 117.
    Detera-Wadleigh S. D. (2001) Lithium-related genetics of bipolar disorder. Ann. Med. 33, 272–285.PubMedGoogle Scholar
  118. 118.
    Dixon A. K., Huber C., and Lowe D. A. (1994) Clozapine promotes approach-oriented behavior in male mice. J. Clin. Psychiatry 55(Suppl B), 4–7.PubMedGoogle Scholar
  119. 119.
    Sakimura K., Kutsuwada T., Ito I., Manabe T., Takayama C., Kushiya E., et al. (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature 373, 151–155.PubMedGoogle Scholar
  120. 120.
    Forrest D., Yuzaki M., Soares H. D., Ng L., Luk D. C., Sheng M., et al. (1994) Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron 13, 325–338.PubMedGoogle Scholar
  121. 121.
    Li Y., Erzurumlu R. S., Chen C., Jhaveri S., and Tonegawa S. (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76, 427–437.PubMedGoogle Scholar
  122. 122.
    Ebralidze A. K., Rossi D. J., Tonegawa S., and Slater N. T. (1996) Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2C gene. J. Neurosci. 16, 5014–5025.PubMedGoogle Scholar
  123. 123.
    Kutsuwada T., Sakimura K., Manabe T., Takayama C., Katakura N., Kushiya E., et al. (1996) Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice. Neuron 16, 333–344.PubMedGoogle Scholar
  124. 124.
    Das S., Sasaki Y. F., Rothe T., Premkumar L. S., Takasu M., Crandall J. E., et al. (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393, 377–381.PubMedGoogle Scholar
  125. 125.
    Sprengel R. and Single F. N. (1999) Mice with genetically modified NMDA and AMPA receptors. Ann. NY Acad. Sci. 868, 494–501.PubMedGoogle Scholar
  126. 126.
    Aiba A., Kano M., Chen C., Stanton M. E., Fox G. D., Herrup K., et al. (1994) Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell 79, 377–388.PubMedGoogle Scholar
  127. 127.
    Masu M., Iwakabe H., Tagawa Y., Miyoshi T., Yamashita M., Fukuda Y., et al. (1995) Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 80, 757–765.PubMedGoogle Scholar
  128. 128.
    Pekhletski R., Gerlai R., Overstreet L. S., Huang X. P., Agopyan N., Slater N. T., et al. (1996) Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. J. Neurosci. 16, 6364–6373.PubMedGoogle Scholar
  129. 129.
    Jia Z., Agopyan N., Miu P., Xiong Z., Henderson J., Gerlai R., et al. (1996) Enhanced LTP in mice deficient in the AMPA receptor GluR2. Neuron 17, 945–956.PubMedGoogle Scholar
  130. 130.
    Lu Y. M., Jia Z., Janus C., Henderson J. T., Gerlai R., Wojtowicz J. M., and Roder J. C. (1997) Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J. Neurosci. 17, 5196–5205.PubMedGoogle Scholar
  131. 131.
    Mulle C., Sailer A., Perez-Otano I., Dickinson-Anson H., Castillo P. E., Bureau I., et al. (1998) Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 392, 601–605.PubMedGoogle Scholar
  132. 132.
    Zamanillo D., Sprengel R., Hvalby O., Jensen V., Burnashev N., Rozov A., et al. (1999) Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284, 1805–1811.PubMedGoogle Scholar
  133. 133.
    Contractor A., Swanson G. T., Sailer A., O’Gorman S., and Heinemann S. F. (2000) Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J. Neurosci. 20, 8269–8278.PubMedGoogle Scholar
  134. 134.
    Huettner J. E. (2001) Kainate receptors: knocking out plasticity. Trends Neurosci. 24, 365–366.PubMedGoogle Scholar
  135. 135.
    Paarmann I., Frermann D., Keller B. U., and Hollmann M. (2000) Expression of 15 glutamate receptor subunits and various splice variants in tissue slices and single neurons of brainstem nuclei and potential functional implications. J. Neurochem. 74, 1335–1345.PubMedGoogle Scholar
  136. 136.
    Meador-Woodruff J. H. and Healy D. J. (2000) Glutamate receptor expression in schizophrenic brain. Brain Res. Brain Res. Rev. 31, 288–294.PubMedGoogle Scholar
  137. 137.
    Ibrahim H. M., Healy D. J., Hogg A. J., Jr., and Meador-Woodruff J. H. (2000) Nucleus-specific expression of ionotropic glutamate receptor subunit mRNAs and binding sites in primate thalamus. Brain Res. Mol. Brain Res. 79, 1–17.PubMedGoogle Scholar
  138. 138.
    Porter R. H., Eastwood S. L., and Harrison P. J. (1997) Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Res. 751, 217–231.PubMedGoogle Scholar
  139. 139.
    Sokolov B. P. (1998) Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of “neuroleptic-free” schizophrenics: evidence on reversible up-regulation by typical neuroleptics. J. Neurochem. 71, 2454–2464.PubMedGoogle Scholar
  140. 140.
    Ibrahim H. M., Hogg A. J., Jr., Healy D. J., Haroutunian V., Davis K. L., and Meador-Woodruff J. H. (2000) Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. Am. J. Psychiatry 157, 1811–1823.PubMedGoogle Scholar
  141. 141.
    Akbarian S., Sucher N. J., Bradley D., Tafazzoli A., Trinh D., Hetrick W. P., et al. (1996) Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J. Neurosci. 16, 19–30.PubMedGoogle Scholar
  142. 142.
    Ohnuma T., Augood S. J., Arai H., McKenna P. J., and Emson P. C. (1998) Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res. Mol. Brain Res. 56, 207–217.PubMedGoogle Scholar
  143. 143.
    Boyer P. A., Skolnick P., and Fossom L. H. (1998) Chronic administration of imipramine and citalopram alters the expression of NMDA receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization study. J. Mol. Neurosci. 10, 219–233.PubMedGoogle Scholar
  144. 144.
    Nowak G., Ordway G. A., and Paul I. A. (1995) Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res. 675, 157–164.PubMedGoogle Scholar
  145. 145.
    Palmer A. M., Burns M. A., Arango V., and Mann J. J. (1994) Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls. J. Neural. Transm. Gen. Sect. 96, 1–8.PubMedGoogle Scholar
  146. 146.
    Karlsson H., Bachmann S., Schroder J., McArthur J., Torrey E. F., and Yolken R. H. (2001) Retroviral RNA identified in the cere-brosprnal fluids and brains of individuals with schizophrenia. Proc. Natl. Acad. Sci. USA 98, 4634–4639.PubMedGoogle Scholar
  147. 147.
    Coyle J. T. (1996) The glutamatergic dysfunction hypothesis for schizophrenia. Harv. Rev. Psychiatry 3, 241–253.PubMedGoogle Scholar
  148. 148.
    Ohtsuki T., Sakurai K., Dou H., Toru M., Yamakawa-Kobayashi K., and Arinami T. (2001) Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia. Mol. Psychiatry 6, 211–216.PubMedGoogle Scholar
  149. 149.
    Rice S. R., Niu N., Berman D. B., Heston L. L., and Sobell J. L. (2001) Identification of single nucleotide polymorphisms (SNPs) and other sequence changes and estimation of nucleotide diversity in coding and flanking regions of the NMDAR1 receptor gene in schizophrenic patients. Mol. Psychiatry 6, 274–284.PubMedGoogle Scholar
  150. 150.
    Nishiguchi N., Shirakawa O., Ono H., Hashimoto T., and Maeda K. (2000) Novel polymorphism in the gene region encoding the carboxyl-terminal intracellular domain of the NMDA receptor 2B subunit: analysis of association with schizophrenia. Am. J. Psychiatry 157, 1329–1331.PubMedGoogle Scholar
  151. 151.
    Sakurai K., Toru M., Yamakawa-Kobayashi K., and Arinami T. (2000) Mutation analysis of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia. Neurosci. Lett. 296, 168–170.PubMedGoogle Scholar
  152. 152.
    Fitzjohn S. M., Irving A. J., Palmer M. J., Harvey J., Lodge D., and Collingridge G. L. (1996) Activation of group I mGluRs potentiates NMDA responses in rat hippocampal slices. Neurosci. Lett. 203, 211–213.PubMedGoogle Scholar
  153. 153.
    Bolonna A. A., Kerwin R. W., Munro J., Arranz M. J., and Makoff A. J. (2001) Polymorphisms in the genes for mGluR types 7 and 8: association studies with schizophrenia. Schizophr. Res. 47, 99–103.PubMedGoogle Scholar
  154. 154.
    Devon R. S., Anderson S., Teague P. W., Muir W. J., Murray V., Pelosi A. J., et al. (2001) The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. Mol. Psychiatry 6, 311–314.PubMedGoogle Scholar
  155. 155.
    Joo A., Shibata H., Ninomiya H., Kawasaki H., Tashiro N., and Fukumaki Y. (2001) Structure and polymorphisms of the human metabotropic glutamate receptor type 2 gene (GRM2): analysis of association with schizophrenia. Mol. Psychiatry, 6, 186–192.PubMedGoogle Scholar
  156. 156.
    Muir W. J., Gosden C. M., Brookes A. J., Fantes J., Evans K. L., Maguire S. M., et al. (1995) Direct microdissection and microcloning of a translocation breakpoint region, t(1;11)(q42.2;q21), associated with schizophrenia. Cytogenet. Cell Genet. 70, 35–40.PubMedGoogle Scholar
  157. 157.
    Fletcher J. M., Evans K., Baillie D., Byrd P., Hanratty D., Leach S., et al. (1993) Schizophrenia-associated chromosome 11q21 translocation: identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources. Am. J. Hum. Genet. 52, 478–490.PubMedGoogle Scholar
  158. 158.
    Semple C. A., Devon R. S., Le Hellard S., and Porteous D. J. (2001) Identification of genes from a schizophrenia-linked translocation breakpoint region. Genomics 73, 123–126.PubMedGoogle Scholar
  159. 159.
    Alagarsamy S., Marino M. J., Rouse S. T., Gereau R. W. T., Heinemann S. F., and Conn P. J. (1999) Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat. Neurosci. 2, 234–240.PubMedGoogle Scholar
  160. 160.
    Neale J. H., Bzdega T., and Wroblewska B. (2000) N-Acetylaspartylglutamate: the most abundant peptide neurotransmitter in the mammalian central nervous system. J. Neurochem. 75, 443–452.PubMedGoogle Scholar
  161. 161.
    Tsai G., Passani L. A., Slusher B. S., Carter R., Baer L., Kleinman J. E., and Coyle J. T. (1995) Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch. Gen. Psychiatry 52, 829–836.PubMedGoogle Scholar
  162. 162.
    Chen A. C., Kalsi G., Brynjolfsson J., Sigmundsson T., Curtis D., Butler R., et al. (1997) Exclusion of linkage of schizophrenia to the gene for the glutamate GluR5 receptor. Biol. Psychiatry 41, 243–245.PubMedGoogle Scholar
  163. 163.
    Chen A. C., Kalsi G., Brynjolfsson J., Sigmundsson T., Curtis D., Butler R., et al. (1996) Lack of evidence for close linkage of the glutamate GluR6 receptor gene with schizophrenia. Am. J. Psychiatry 153, 1634–1636.PubMedGoogle Scholar
  164. 164.
    Noga J. T., Hyde T. M., Herman M. M., Spurney C. F., Bigelow L. B., Weinberger D. R., and Kleinman J. E. (1997) Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains. Synapse 27, 168–176.PubMedGoogle Scholar
  165. 165.
    Freed W. J., Dillon-Carter O., and Kleinman J. E. (1993) Properties of [3H]AMPA binding in postmortem human brain from psychotic subjects and controls: increases in caudate nucleus associated with suicide. Exp. Neurol. 121, 48–56.PubMedGoogle Scholar
  166. 166.
    Gecz J., Barnett S., Liu J., Hollway G., Donnelly A., Eyre H., et al. (1999) Characterization of the human glutamate receptor subunit 3 gene (GRIA3), a candidate for bipolar disorder and nonspecific X-linked mental retardation. Genomics 62, 356–368.PubMedGoogle Scholar
  167. 167.
    Rice J. P., Saccone N. L., and Rasmussen E. (2001) Definition of the phenotype. Adv. Genet. 42, 69–76.PubMedGoogle Scholar
  168. 168.
    Sachidanandam R., Weissman D., Schmidt S. C., Kakol J. M., Stein L. D., Marth G., et al. (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409, 928–933.PubMedGoogle Scholar
  169. 169.
    Baron M. (2001) Genetics of schizophrenia and the new millennium: progress and pitfalls. Am. J. Hum. Genet. 68, 299–312.PubMedGoogle Scholar
  170. 170.
    Thaker G. K. and Carpenter W. T., Jr. (2001) Advances in schizophrenia. Nat. Med. 7, 667–671.PubMedGoogle Scholar
  171. 171.
    Kato T. (2001) Molecular genetics of bipolar disorder. Neurosci. Res. 40, 105–113.PubMedGoogle Scholar
  172. 172.
    Todd R. D. and Botteron K. N. (2001) Family, genetic, and imaging studies of early-onset depression. Child. Adolesc. Psychiatr Clin. North Am. 10, 375–390.Google Scholar
  173. 173.
    Kornberg J. R., Brown J. L., Sadovnick A. D., Remick R. A., Keck P. E., Jr., McElroy S. L., et al. (2000) Evaluating the parent-of-origin effect in bipolar affective disorder. Is a more penetrant subtype transmitted paternally? J. Affect. Disord. 59, 183–192.PubMedGoogle Scholar
  174. 174.
    Ohara K. (2001) Anticipation, imprinting, trinucleotide repeat expansions and psychoses. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 167–192.PubMedGoogle Scholar
  175. 175.
    Keverne E. B. (1997) Genomic imprinting in the brain. Curr. Opin. Neurobiol. 7, 463–468.PubMedGoogle Scholar
  176. 176.
    Reik W. and Walter J. (2001) Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21–32.PubMedGoogle Scholar
  177. 177.
    Latham K. E. (1999) Epigenetic modification and imprinting of the mammalian genome during development. Curr. Top. Dev. Biol. 43, 1–49.PubMedGoogle Scholar
  178. 178.
    Nadeau J. H. (2001) Modifier genes in mice and humans. Nat. Rev. Genet. 2, 165–174.PubMedGoogle Scholar
  179. 179.
    Falls J. G., Pulford D. J., Wylie A. A., and Jirtle R. L. (1999) Genomic imprinting: implications for human disease. Am. J. Pathol. 154, 635–647.PubMedGoogle Scholar
  180. 180.
    Morison I. M., Paton C. J., and Cleverley S. D. (2001) The imprinted gene and parent-of-origin effect database. Nucleic Acids Res. 29, 275–276.PubMedGoogle Scholar
  181. 181.
    Constancia M., Pickard B., Kelsey G., and Reik W. (1998) Imprinting mechanisms. Genome Res. 8, 881–900.PubMedGoogle Scholar
  182. 182.
    Mowry B. J. and Nancarrow D. J. (2001) Molecular genetics of schizophrenia. Clin. Exp. Pharmacol. Physiol. 28, 66–69.PubMedGoogle Scholar
  183. 183.
    Warrington J. A., Bailey S. K., Armstrong E., Aprelikova O., Alitalo K., Dolganov G. M., et al. (1992) A radiation hybrid map of 18 growth factor, growth factor receptor, hormone receptor, or neurotransmitter receptor genes on the distal region of the long arm of chromosome 5. Genomics 13, 803–808.PubMedGoogle Scholar
  184. 184.
    Puckett C., Gomez C. M., Korenberg J. R., Tung H., Meier T. J., Chen X. N., and Hood L. (1991) Molecular cloning and chromosomal localization of one of the human glutamate receptor genes. Proc. Natl. Acad. Sci. USA 88, 7557–7561.PubMedGoogle Scholar
  185. 185.
    Sun W., Ferrer-Montiel A. V., Schinder A. F., McPherson J. P., Evans G. A., and Montal M. (1992) Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. Proc. Natl. Acad. Sci. USA 89, 1443–1447.PubMedGoogle Scholar
  186. 186.
    McNamara J. O., Eubanks J. H., McPherson J. D., Wasmuth J. J., Evans G. A., and Heinemann S. F. (1992) Chromosomal localization of human glutamate receptor genes. J. Neurosci. 12, 2552–2562.Google Scholar
  187. 187.
    Hu W., Zuo J., De Jager P. L., and Heintz N. (1998) The human glutamate receptor delta 2 gene (GRID2) maps to chromosome 4q22. Genomics 47, 143–145.PubMedGoogle Scholar
  188. 188.
    Gregor P., Gaston S. M., Yang X., O’Regan J. P., Rosen D. R., Tanzi R. E., et al. (1994) Genetic and physical mapping of the GLUR5 glutamate receptor gene on human chromosome 21. Hum. Genet. 94, 565–570.PubMedGoogle Scholar
  189. 189.
    Eubanks J. H., Puranam R. S., Kleckner N. W., Bettler B., Heinemann S. F., and McNamara J. O. (1993) The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1–22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 90, 178–182.PubMedGoogle Scholar
  190. 190.
    Sander T., Janz D., Ramel C., Ross C. A., Paschen W., Hildmann T., et al. (1995) Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies. Neurology 45, 1713–1720.PubMedGoogle Scholar
  191. 191.
    Paschen W., Blackstone C. D., Huganir R. L., and Ross C. A. (1994) Human GluR6 kainate receptor (GRIK2): molecular cloning, expression, polymorphism, and chromosomal assignment. Genomics 20, 435–440.PubMedGoogle Scholar
  192. 192.
    Puranam R. S., Eubanks J. H., Heinemann S. F., and McNamara J. O. (1993) Chromosomal localization of gene for human glutamate receptor subunit-7. Somat. Cell Mol. Genet. 19, 581–588.PubMedGoogle Scholar
  193. 193.
    Szpirer C., Molne M., Antonacci R., Jenkins N. A., Finelli P., Szpirer J., et al. (1994) The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proc. Natl. Acad. Sci. USA 91, 11849–11853.PubMedGoogle Scholar
  194. 194.
    Brett P. M., Le Bourdelles B., See C. G., Whiting P. J., Attwood J., Woodward K., et al. (1994) Genomic cloning and localization by FISH and linkage analysis of the human gene encoding the primary subunit NMDAR1 (GRIN1) of the NMDA receptor channel. Ann. Hum. Genet. 58, 95–100.PubMedGoogle Scholar
  195. 195.
    Karp S. J., Masu M., Eki T., Ozawa K., and Nakanishi S. (1993) Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor. J. Biol. Chem. 268, 3728–3733.PubMedGoogle Scholar
  196. 196.
    Collins C., Duff C., Duncan A. M., Planells-Cases R., Sun W., Norremolle A., et al. (1993) Mapping of the human NMDA receptor subunit (NMDAR1) and the proposed NMDA receptor glutamate-binding subunit (NMDARA1) to chromosomes 9q34.3 and chromosome 8, respectively. Genomics 17, 237–239.PubMedGoogle Scholar
  197. 197.
    Takano H., Onodera O., Tanaka H., Mori H., Sakimura K., Hori T., et al. (1993) Chromosomal localization of the epsilon 1, epsilon 3 and zeta 1 subunit genes of the human NMDA receptor channel. Biochem. Biophys. Res. Commun. 197, 922–926.PubMedGoogle Scholar
  198. 198.
    Kalsi G., Whiting P., Bourdelles B. L., Callen D., Barnard E. A., and Gurling H. (1998) Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels. Genomics 47, 423–425.PubMedGoogle Scholar
  199. 199.
    Mandich P., Schito A. M., Bellone E., Antonacci R., Finelli P., Rocchi M., and Ajmar F. (1994) Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12. Genomics 22, 216–218.PubMedGoogle Scholar
  200. 200.
    Stephan D., Bon C., Holzwarth J. A., Galvan M., and Pruss R. M. (1996) Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants. Neuropharmacology 35, 1649–1660.PubMedGoogle Scholar
  201. 201.
    Ganesh S., Amano K., and Yamakawa K. (2000) Assignment of the gene GRM1 coding for metabotropic glutamate receptor 1 to human chromosome band 6q24 by in situ hybridization. Cytogenet. Cell Genet. 88, 314–315.PubMedGoogle Scholar
  202. 202.
    Flor P. J., Lindauer K., Puttner I., Ruegg D., Lukic S., Knopfel T., and Kuhn R. (1995) Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2. Eur. J. Neurosci. 7, 622–629.PubMedGoogle Scholar
  203. 203.
    Scherer S. W., Duvoisin R. M., Kuhn R., Heng H. H., Belloni E., and Tsui L. C. (1996) Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 31, 230–233.PubMedGoogle Scholar
  204. 204.
    Barbon A., Ferraboli S., and Barlati S. (2000) Assignment of the human metabotropic glutamate receptor gene GRM4 to chromosome 6 band p21.3 by radiation hybrid mapping. Cytogenet. Cell Genet. 88, 210.PubMedGoogle Scholar
  205. 205.
    Devon R. S. and Porteous D. J. (1997) Physical mapping of a glutamate receptor gene in relation to a balanced translocation associated with schizophrenia in a large Scottish family. Psychiatr. Genet. 7, 165–169.PubMedGoogle Scholar
  206. 206.
    Hashimoto T., Inazawa J., Okamoto N., Tagawa Y., Bessho Y., Honda Y., and Nakanishi S. (1997) The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6. Eur. J. Neurosci. 9, 1226–1235.PubMedGoogle Scholar
  207. 207.
    Barbon A., Ferraboli S., and Barlati S. (2000) Assignment of the human metabotropic glutamate receptor gene GRM7 to chromosome 3p26.1→p25.2 by radiation hybrid mapping. Cytogenet. Cell Genet. 88, 288.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  1. 1.Molecular Neurobiology LaboratorySalk Institute for Biological StudiesLa Jolla

Personalised recommendations