, Volume 111, Issue 4, pp 391–401 | Cite as

Glutamate: its role in learning, memory, and the aging brain

  • William J. McEntee
  • Thomas H. Crook


l-Glutamate is the most abundant of a group of endogenous amino acids in the mammalian central nervous system which presumably function as excitatory neurotransmitters and under abnormal conditions may behave as neurotoxins. As neurotransmitters, these compounds are thought to play an important role in functions of learning and memory. As neurotoxins, they are believed to be involved in the pathogenesis of a variety of neurodegenerative disorders in which cognition is impaired. Moreover, brain structures which are considered anatomical substrata for learning and memory may be particularly vulnerable to the neurotoxic actions of these excitatory amino acids, especially in the elderly who are also the segment of the population most susceptible to impairments of mnemonic function. This paper is a review of data concerning the role of excitatory amino acids in the processes of learning and memory and in the pathogenesis and treatment of disorders thereof.

Key words

Glutamate Memory Excitotoxin Aging N-methyl-d-aspartate 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alger BE, Teyler TJ (1976) Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice. Brain Res 110:463–480CrossRefPubMedGoogle Scholar
  2. Allen HL, Iversen LL (1990) Phencyclidine, dizocilpine, and cerebrocortical neurons. Science 247:221PubMedGoogle Scholar
  3. Ambrozi L, Danielczyk W (1988) Treatment of impaired cerebral function in psychogeriatric patients with memantine — results of a phase II double-blind study. Pharmacopsychiatry 21:144–146PubMedGoogle Scholar
  4. Aprikyan GV, Gekchyan KG (1988) Release of neurotransmitter amino acids from rat brain synaptosomes. Gerontology 34:35–40PubMedGoogle Scholar
  5. Ascher P, Nowak L (1988) Quisqualate- and kainate-activated channels in mouse central neurones in culture. J Physiol 399:227–246PubMedGoogle Scholar
  6. Banay-Schwartz M, Lajtha A, Palkovits M (1989) Changes with ageing in the levels of amino acids in rat CNS structural elements. I. Glutamate and related amino acids. Neurochem Res 14:555–562CrossRefPubMedGoogle Scholar
  7. Bliss TVP, Gardner-Medwin AR (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetised rabbit following stimulation of the perforant path. J Physiol 232:357–374PubMedGoogle Scholar
  8. Bliss TVP, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetised rabbit following stimulation of the perforant path. J Physiol 232:331–356PubMedGoogle Scholar
  9. Bliss TVP, Lynch MA (1988) Long-term potentiation of synaptic transmission in the hippocampus: properties and mechanisms. Neurol Neurobiol 35:3–72Google Scholar
  10. Bonhaus DW, Perry WB, McNamara JO (1990) Decreased density, but not number, of N-methyl-d-aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats. Brain Res 532:82–86CrossRefPubMedGoogle Scholar
  11. Bormann J (1989) Nemantine is a potent blocker of N-methyl-d-aspartate (NMDA) receptor channels. Eur J Pharmacol 166:591–592CrossRefPubMedGoogle Scholar
  12. Bowen DM, Francis PT, Procter AW, Young AB (1992) Treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry 55:328Google Scholar
  13. Bridges RJ, Nieto-Sampedro M, Kadri M, Cotman CW (1987) A novel chloride-dependentl-[3H]glutamate binding site in astrocyte membranes. J Neurochem 48:1709–1715PubMedGoogle Scholar
  14. Brierly JB, Graham DI (1984) Hypoxia and vascular disorders of the central nervous system. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's neuropathology. Wiley, New York, pp 125–207Google Scholar
  15. Brown TH, Chapman PF, Kairis EW, Keenan CL (1988) Long-term synaptic potentiation. Science 242:724–728PubMedGoogle Scholar
  16. Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8:189–198CrossRefPubMedGoogle Scholar
  17. Butterworth RF (1986) Cerebral thiamine-dependent enzyme changes in experimental Wernicke's encephalopathy. Metab Brain Dis 1:165–175CrossRefPubMedGoogle Scholar
  18. Butterworth RF (1982) Neurotransmitter function in thiamine deficiency encephalopathy. Neurochem Int 4:449–464CrossRefGoogle Scholar
  19. Butterworth RF, Hamel E, Landreville F, Barbeau A (1979) Amino acid changes in thiamine-deficient encephalopathy: some implications for the pathogenesis of Friedreich's ataxia. Can J Neurol Sci 6:217–222PubMedGoogle Scholar
  20. Chen H-SV, Pellegrini JW, Aggarwal SK, Lei SZ, Lipton SA (1992) Open-channel block of N-methyl-d-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated toxicity. J Neurosci 12:4427–4436PubMedGoogle Scholar
  21. Choi DW (1985) Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci Lett 58:293–297CrossRefPubMedGoogle Scholar
  22. Choi DW (1987) Ionic dependence of glutamate neurotoxicity in cortical cell culture. J Neurosci 7:369–379PubMedGoogle Scholar
  23. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634CrossRefPubMedGoogle Scholar
  24. Choi DW (1989) Non-NMDA receptor-mediated neuronal injury in Alzheimer's disease. Neurobiol Aging 10:605–606CrossRefPubMedGoogle Scholar
  25. Choi DW, Peters S, Visekul V (1987) Dextrorphan and levorphanol selectively block N-methyl-d-aspartate receptor-mediated neurotoxicity on cortical neurons. J Pharmacol Exp Ther 242:713–720PubMedGoogle Scholar
  26. Collingridge GL, Bliss TVP (1987) NMDA receptors — their role in long-term potentiation. TINS 10:288–293Google Scholar
  27. Collingridge GL, Lester RAJ (1989) Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 40:143–210Google Scholar
  28. Collingridge GL, Kehl SJ, McLennan H (1983) Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol (Lond) 334:33–46PubMedGoogle Scholar
  29. Cotman CW, Monaghan DT, Ottersen OP, Storm-Mathisen J (1987) Anatomical organization of excitatory amino acid receptors and their pathways. TINS 10:273–280Google Scholar
  30. Cotman CW, Geddes JW, Bridges RJ, Monaghan DT (1989) N-methyl-d-aspartate receptors and Alzheimer's disease. Neurobiol Aging 10:603–605CrossRefPubMedGoogle Scholar
  31. Crook T, Bartus RT, Ferris SH, Whitehouse P, Cohen GD, Gershon S (1986) Age-associated memory impairment. Proposed diagnostic criteria and measures of clinical change: report of a National Institute of Mental Health work group. Dev Neuropsychol 2:261–276Google Scholar
  32. David P, Lusky M, Teichberg VI (1988) Involvement of excitatory neurotransmitters in the damage produced in chick embryo retinas by anoxia and extracellular high potassium. Exp Eye Res 46:657–662PubMedGoogle Scholar
  33. Davies SN, Alford ST, Coan EJ, Lester RAJ, Collingridge GL (1988) Ketamine blocks an NMDA receptor-mediated component of synaptic transmission in rat hippocampus in a voltage-dependent manner. Neurosci Lett 92:213–217CrossRefPubMedGoogle Scholar
  34. Davies SN, Lester RAJ, Collingridge GL (1989) Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation. Nature 338:500–503CrossRefPubMedGoogle Scholar
  35. Dawson R Jr, Wallace DR, Meldrum MJ (1989) Endogenous glutamate release from frontal cortex of adult and aged rats. Neurobiol Aging 10:665–668CrossRefPubMedGoogle Scholar
  36. deKoning-Verst IF (1980) Glutamate metabolism in aging rat brain. Mech Aging Dev 13:83–92CrossRefPubMedGoogle Scholar
  37. Deutsch SI, Morihisa JM (1988) Glutamatergic abnormalities in Alzheimer's disease and a rationale for clinical trials withl-glutamate. Clin Neuropharmacol 11:18–35PubMedGoogle Scholar
  38. Douglas RM, Goddard GV (1975) Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res 86:205–215CrossRefPubMedGoogle Scholar
  39. Flood JF, Baker ML, Davis JL (1990) Modulation of memory processing by glutamic acid receptor agonists and antagonists. Brain Res 521:197–202CrossRefPubMedGoogle Scholar
  40. Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42:1–11PubMedGoogle Scholar
  41. Foster NL, Giordani B, Mellow A, Aronson S, Berent S (1991) Memory effect of low-dose ketamine in Alzheimer's disease. Neurology 41 [Suppl 1]:214Google Scholar
  42. Gaitonde MK, Fayein NA, Johnson AL (1975) Decreased metabolism in vivo of glucose into amino acids of the brain of thiamine deficient rats after treatment with pyrithiamine. J Neurochem 24:1215–1223PubMedGoogle Scholar
  43. Garthwaite G, Garthwaite J (1986) Neurotoxicity of excitatory amino acid receptor agonists in rat cerebellar slices. Dependence on calcium concentration. Neurosci Lett 66:193–198CrossRefPubMedGoogle Scholar
  44. Gilbertson TA, Scobey R, Wilson M (1991) Permeation of calcium ions through non-NMDA glutamate channels in retinal bipolar cells. Science 251:1613–1615PubMedGoogle Scholar
  45. Gill R, Foster A, Woodruff GN (1987) Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7:3343–3349PubMedGoogle Scholar
  46. Greenamyre JT (1986) The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 43:1058–1063PubMedGoogle Scholar
  47. Greenamyre JT, Young AB (1989) Excitatory amino acids and Alzheimer's disease. Neurobiol Aging 10:593–602CrossRefPubMedGoogle Scholar
  48. Handelmann GE, Contreras PC, O'Donohue TL (1987) Selective memory impairment by phencyclidine in rats. Eur J Pharmacol 140:69–73CrossRefPubMedGoogle Scholar
  49. Handelmann GE, Nevins ME, Mueller LL, Arnolde SM, Cordi AA (1989) Milacemide, a glycine prodrug, enhances performance of learning tasks in normal and amnesic rodents. Pharmacol Biochem Behav 34:823–828Google Scholar
  50. Harris EW, Cotman CW (1986) Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl-d-aspartate antagonists. Neurosci Lett 70:132–137CrossRefPubMedGoogle Scholar
  51. Himwich WA (1973) Neurobiological aspects of maturation and ageing. In: Ford DH (ed) Progress in brain research. Elsevier, New York, pp 13–25Google Scholar
  52. Honey CR, Miljkovic Z, Macdonald JF (1985) Ketamine and phencyclidine cause a voltage-dependent block of responses tol-aspartic acid. Neurosci Lett 61:135–139CrossRefPubMedGoogle Scholar
  53. Hood WF, Compton RP, Monahan JB (1989)d-Cycloserine: a ligand for the N-methyl-d-aspartate coupled glycine receptor has partial agonist characteristics. Neurosci Lett 98:91–95CrossRefPubMedGoogle Scholar
  54. Huettner JE, Bean BP (1988) Block of N-methyl-d-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. Proc Natl Acad Sci USA 85:1307–1311PubMedGoogle Scholar
  55. Hume RI, Dingledine R, Heinemann SF (1991) Identification of a site in glutamate receptor subunits that controls calcium permeability. Science 253:1028–1031PubMedGoogle Scholar
  56. Iino M, Ozakawa K, Tsuzuki K (1990) Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J Physiol 424:151–165PubMedGoogle Scholar
  57. Irle E, Markowitsch HJ (1983) Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin-B1 deficiency. Behav Brain Res 9:277–294CrossRefPubMedGoogle Scholar
  58. Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531CrossRefPubMedGoogle Scholar
  59. Kauer JA, Nicoll RA (1988) An APV-resistant non-associative form of long-term potentiation in the rat hippocampus. In: Haas HL, Buzsaki G (eds) Synaptic plasticity in the hippocampus. Springer, Berlin Heidelberg New YorkGoogle Scholar
  60. Kemp JA, Foster AC, Wong EHF (1987) Non-competitive antagonists of excitatory amino acid receptors. TINS 10:294–298Google Scholar
  61. Kito S, Miyoshi R, Nomoto T (1990) Influence of age on NMDA receptor complex in rat brain studies by in vitro autoradiography. J Histochem Cytochem 38:1725–1731PubMedGoogle Scholar
  62. Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDA receptors expressed in Xenopus oocytes. Science 241:835–837PubMedGoogle Scholar
  63. Kochhar A, Zivin JA, Lyden PD, Mazzarella V (1988) Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia. Arch Neurol 45:148–153PubMedGoogle Scholar
  64. Kornhuber J, Bormann J, Retz W, Hubers M, Riederer P (1989) Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 166:589–590CrossRefPubMedGoogle Scholar
  65. Kral VA (1962) Senescent forgetfulness: benign and malignant. J Can Med Assoc 86:257–260Google Scholar
  66. Langlais PJ, Mair RG (1990) Protective effects of the glutamate antagonist MK-801 on pyrithiamine-induced lesions and amino acid changes in rat brain. J Neurosci 10:1664–1674PubMedGoogle Scholar
  67. Langlais PJ, Mair RG, Anderson CD, McEntee WJ (1988) Long-lasting changes in regional brain amino acids and monoamines in recovered pyrithiamine treated rats. Neurochem Res 13:1199–1206CrossRefPubMedGoogle Scholar
  68. Larrabee GJ, McEntee WJ, Crook TH (1992) Age-associated memory impairment. In: Thal LJ, Moos WH, Gamzu ER (eds) Cognitive disorders: pathophysiology and treatment. Marcel Dekker, New York, pp 291–306Google Scholar
  69. Lodge D, Aram JA, Church J, Davies SN, Martin D, O'Shaugnessy CT, Zeman S (1987) Excitatory amino acids and phencyclidine like drugs. In: Hicks TP, Lodge D, McLennan H (eds) Neurology and neurobiology, vol 24. Excitatory amino acid transmission. Liss, New York, pp 83–90Google Scholar
  70. Lynch G, Baudry M (1984) The biochemistry of memory: a new and specific hypothesis. Science 224:1057–1063Google Scholar
  71. Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F (1983) Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305:719–721CrossRefPubMedGoogle Scholar
  72. Mair RG, Anderson CD, Langlais PJ, McEntee WJ (1988) Behavioral impairments, brain lesions and monoaminergic activity in the rat following recovery from a bout of thiamine deficiency. Behav Brain Res 27:223–239CrossRefPubMedGoogle Scholar
  73. Mamounas LA, Thompson RF, Lynch G, Baudry M (1984) Classical conditioning of the rabbit eyelid response increases glutamate receptor binding in hippocampal synaptic membranes. Proc Natl Acad Sci USA 81:2548–2552PubMedGoogle Scholar
  74. Maragos WF, Greenamyre JT, Penney JB Jr, Young AB (1987) Glutamate dysfunction in Alzheimer's disease; an hypothesis. TINS 10:65–68Google Scholar
  75. Mayer ML, Westbrook GL (1985) The action of N-methyl-d-aspartate acid on mouse spinal neurones in culture. J Physiol 361:65–90PubMedGoogle Scholar
  76. Mayer ML, Westbrook GL (1987) Permeation and block of N-methyl-d-aspartatic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol 394:501–527PubMedGoogle Scholar
  77. Mayer ML, Westbrook GL, Vyklicky L (1988) Sites of antagonist action on N-methyl-d-aspartatic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J Neurophysiol 60:645–663PubMedGoogle Scholar
  78. McDonald JW, Silverstein FS, Johnston MV (1987) MK-801 protects the neonatal brain from hypoxic-ischemic damage. Eur J Pharmacol 140:359–361CrossRefPubMedGoogle Scholar
  79. McEntee WJ, Mair RG (1990) The Korsakoff syndrome: a neurochemical perspective. TINS 13:340–344PubMedGoogle Scholar
  80. McLamb RL, Williams LR, Nanry KP, Wilson WA, Tilson HA (1990) MK-801 impedes the acqisition of a spatial memory task in rats. Pharmacol Biochem Behav 37:41–45Google Scholar
  81. Miyoshi R, Kito S, Doudou N, Nomoto T (1990) Age-related changes of strychnine-insensitive glycine receptors in rat brain as studied by in vitro autoradiography. Synapse 6:338–343CrossRefPubMedGoogle Scholar
  82. Monaghan DT, Cotman CW (1986) Distribution of N-methyl-d-aspartate-sensitivel-[3H]glutamate binding sites in rat brain. J Neurosci 5:2909–2919Google Scholar
  83. Monahan JB, Handelmann GE, Hood WF, Cordi AA (1989)d-Cycloserine, a positive modulator of the N-methyl-d-aspartate receptor, enhances performance of learning tasks in rats. Pharmacol Biochem Behav 34:649–653CrossRefPubMedGoogle Scholar
  84. Mondadori C, Weiskrantz L, Buerki H, Petschke F, Fagg GE (1989) NMDA receptor antagonists can enhance or impair learning performance in animals. Exp Brain Res 75:449–456CrossRefPubMedGoogle Scholar
  85. Mooradian AD (1988) Effect of aging on the blood-brain barrier. Neurobiol Aging 9:31–39PubMedGoogle Scholar
  86. Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation of an N-methyl-d-aspartate receptor antagonist, AP5. Nature 319:774–776Google Scholar
  87. Najlerahim A, Francis PT, Bowen DM (1990) Age-related alteration in excitatory amino acid neurotransmission in rat brain. Neurobiol Aging 11:155–158CrossRefPubMedGoogle Scholar
  88. Nicoll RA, Kauer JA, Malenka RC (1988) The current excitement in long-term potentiation. Neuron 1:97–103CrossRefPubMedGoogle Scholar
  89. Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Glutamate becomes neurotoxic via the N-methyl-d-aspartate receptor when intracellular energy levels are reduced. Brain Res 451:205–212CrossRefPubMedGoogle Scholar
  90. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz Z (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307:462–465Google Scholar
  91. Olney JW (1989) Excitatory amino acids and neuropsychiatric disorders. Biol Psychiatry 26:505–525CrossRefPubMedGoogle Scholar
  92. Olney JW, Ho OL, Rhee V (1971) Cytotoxic effects of acidic and sulfur-containing amino acids on the infant mouse central nervous system. Exp Brain Res 14:61–76CrossRefPubMedGoogle Scholar
  93. Olney JW, Price MT, Samson L, Labruyere J (1986) The role of specific ions in glutamate neurotoxicity. Neurosci Lett 65:65–71CrossRefPubMedGoogle Scholar
  94. Olney JW, Ikonomidou C, Mosinger JL, Fierdich G (1988) MK-801 prevents hypobaric-ischemic neuronal degeneration in infant rat brain. J Neurosci 9:1701–1704Google Scholar
  95. Olney JW, Labruyere J, Price MT (1989) Pathological changes in cerebrocortical neurons by phencyclidine and related drugs. Science 244:1360–1362Google Scholar
  96. Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA (1991) NMDA antagonist neurotoxicity: mechanism and prevention. Science 254:1515–1518PubMedGoogle Scholar
  97. Parada-Turska J, Turski WA (1990) Excitatory amino acid antagonists and memory: effect of drugs acting at N-methyl-d-aspartate receptors in learning and memory tasks. Neuropharmacology 29:1111–1116CrossRefPubMedGoogle Scholar
  98. Pellegrini JW, Chen H-SV, Lei SZ, Sucher NJ, Lipton SA (1991) Amantadine derivatives prevent NMDA receptor-mediated neurotoxicity. Soc Neurosci Abstr 17:6Google Scholar
  99. Perl TM, Bedard L, Kosatsky T, Hockin JC, Todd ECD, Remis RS (1990) An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. N Engl J Med 322:1775–1780PubMedGoogle Scholar
  100. Peters S, Koh J, Choi DW (1987) Zinc selectively blocks the action of N-methyl-d-aspartate on cortical neurones. Science 236:589–593PubMedGoogle Scholar
  101. Plaitakis A, Berl S, Yahr MD (1984) Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol 15:144–153CrossRefPubMedGoogle Scholar
  102. Price MT, Olney JW, Haft R (1981) Age-related changes in glutamate concentration and synaptosomal glutamate uptake in adult rat striatum. Life Sci 28:1365–1370CrossRefPubMedGoogle Scholar
  103. Procter AW, Palmer AM, Francis PT, Lowe SL (1988) Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease. J Neurochem 50:790–802PubMedGoogle Scholar
  104. Ransom RW, Stec NL (1988) Cooperative modulation at [3H]-MK-801 binding to the NMDA receptor-ion channel complex byl-glutamate, glycine, and polyamines. J Neurochem 51:830–836PubMedGoogle Scholar
  105. Robinson JK, Mair RG (1992) MK-801 protects rats from brain lesions and behavioral impairment following pyrithiamine-induced thiamine deficiency (PTD). Behav Neurosci 106:623–633CrossRefPubMedGoogle Scholar
  106. Robinson TN, Robertson C, Cross AJ, Green AR (1990) Modulation of [3H] dizocilpine ([3H]-MK-801) binding to rat cortical N-methyl-d-aspartate receptors by polyamines. Mol Neuropharmacol 1:31–35Google Scholar
  107. Rothman S (1985) Excitatory amino acid neurotoxicity is produced by passive chloride influx. J Neurosci 6:1884–1891Google Scholar
  108. Schwartz BL, Hashtroudi S, Herting RL, Handerson BA, Deutsch SI (1991) Glycine prodrug facilitates memory retrieval in humans. Neurology 41:1341–1343PubMedGoogle Scholar
  109. Schwartzkroin P, Wester K (1975) Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hippocampal slice. Brain Res 89:107–119CrossRefPubMedGoogle Scholar
  110. Singh L, Oles R, Woodruff GN (1990) In vitro interaction of a polyamine with the NMDA receptor. Eur J Pharmacol 180:391–392CrossRefPubMedGoogle Scholar
  111. Smith CCT, Bowen DM, Davison AN (1983) The evoked release of endogenous amino acids from tissue prisms of human neocortex. Brain Res 269:103–109CrossRefPubMedGoogle Scholar
  112. Sprosen TS, Woodruff GN (1990) Polyamines potentiate NMDA induced whole-cell currents in cultured striatal neurons. Eur J Pharmacol 179:477–478CrossRefPubMedGoogle Scholar
  113. Stewart GR, Zorumski CF, Price MT, Olney JW (1990) Domoic acid: a dementia-inducing excitotoxic food poison with kainic acid receptor specificity. Exp Neurol 110:127–138CrossRefPubMedGoogle Scholar
  114. Tamaru M, Yoneda Y, Ogita K, Shimizu J, Nagata Y (1991) Age-related decreases of the N-methyl-d-aspartate receptor complex in the rat cerebral cortex and hippocampus. Brain Res 542:83–90CrossRefPubMedGoogle Scholar
  115. Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman NR (1990) Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 322:1781–1787PubMedGoogle Scholar
  116. Troncoso JC, Johnson MV, Hess KM, Griffin JW, Price DL (1981) Model of Wernicke's encephalopathy. Arch Neurol 38:350–354PubMedGoogle Scholar
  117. Verdoorn TA, Burnashev N, Monyer H, Seeburg PH, Sakmann B (1991) Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252:1715–1718Google Scholar
  118. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff syndrome. FA Davis, PhiladelphiaGoogle Scholar
  119. Vyklicky L Jr, Krusek J, Edwards C (1988) Differences in the pore sizes of the N-methyl-d-aspartate and kainate cation channels. Neurosci Lett 89:313–318CrossRefPubMedGoogle Scholar
  120. Watkins JC, Krogsgaard-Larsen P, Honore T (1990) Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. TIPS 11:25–33PubMedGoogle Scholar
  121. Watson GB, Bolanowski MA, Baganoff MP, Deppeler CL, Lanthorn TH (1990)d-Cycloserine acts as a partial agonist at the gylcine modulatory site of the NMDA receptor expressed in Xenopus oocytes. Brain Res 510:158–160CrossRefPubMedGoogle Scholar
  122. Wenk GL, Grey CM, Ingram DK, Spangler EL, Olton DS (1989a) Retention of maze performance inversely correlates with NMDA receptor number in hippocampus and frontal neocortex in rat. Behav Neurosci 103:688–690CrossRefPubMedGoogle Scholar
  123. Wenk GL, Pierce DJ, Struble RG, Price DL, Cork LC (1989b) Age-related changes in multiple neurotransmitter systems in the monkey brain. Neurobiol Aging 10:11–19CrossRefPubMedGoogle Scholar
  124. Wenk GL, Walker LC, Price DL, Cork LC (1991) Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys. Neurobiol Aging 12:93–98CrossRefPubMedGoogle Scholar
  125. Westbrook GL, Mayer ML (1987) Micromolar concentrations of Zn2+ antagonise NMDA and GABA responses of hippocampal neurones. Nature 323:640–643CrossRefGoogle Scholar
  126. Wheeler DD (1980) Aging of membrane transport mechanisms in the central nervous system-high affinity glutamic acid transport in rat cortical synaptosomes. Exp Gerontol 15:265–284CrossRefGoogle Scholar
  127. Wheeler DD, Ondo JG (1986) Time course of the aging of the high affinityl-glutamate transporter in rat cortical synaptosomes. Exp Gerontol 21:159–168CrossRefPubMedGoogle Scholar
  128. Williams K, Romano C, Molinoff PB (1989) Effects of polyamines on the binding of [3H] MK-801 to the N-methyl-d-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. Mol Pharmacol 36:575–581PubMedGoogle Scholar
  129. Wisniewski HM, Kozlowski PB (1982) Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT). Ann NY Acad Sci 396:119–129PubMedGoogle Scholar
  130. Wozniak DF, Olney JW, Kettinger L III, Price M, Miller JP (1990) Behavioral effects of MK-801 in the rat. Psychopharmacology 101:47–56Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • William J. McEntee
    • 1
  • Thomas H. Crook
    • 2
  1. 1.Cognitive Research Services Inc.SarasotaUSA
  2. 2.Memory Assessment Clinics Inc.BethesdaUSA

Personalised recommendations