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Glutamate receptor antagonism: neurotoxicity, anti-akinetic effects, and psychosis

  • P. Riederer
  • K. W. Lange
  • J. Kornhuber
  • K. Jellinger
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 34)

Summary

There is evidence to suggest that glutamate and other excitatory amino acids play an important role in the regulation of neuronal excitation. Glutamate receptor stimulation leads to a non-physiological increase of intracellular free Ca2+. Disturbed Ca2+ homeostasis and subsequent radical formation may be decisive factors in the pathogenesis of neurodegenerative diseases.

Decreased glutamatergic activity appears to contribute to paranoid hallucinatory psychosis in schizophrenia and pharmacotoxic psychosis in Parkinson’s disease. It has been suggested that a loss of glutamatergic function causes dopaminergic over-activity. Imbalances of glutamatergic and dopaminergic systems in different brain regions may result in anti-akinetic effects or the occurrence of psychosis. The simplified hypothesis of a glutamatergic- dopaminergic (im)-balance may lead to a better understanding of motor behaviour and psychosis.

Keywords

NMDA Receptor Cerebral Infarction Excitatory Amino Acid Excitatory Amino Acid Receptor Glutamatergic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Benes FM, Davidson J, Bird ED (1986) Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Arch Gen Psychiatry 43: 31–35PubMedCrossRefGoogle Scholar
  2. Danielczyk W (1973) Die Behandlung von akinetischen Krisen. Med Welt 24: 1278PubMedGoogle Scholar
  3. Deakin JWF, Slater P, Simpson MDC, Gilchrist AC, Skan WJ, Royston MC, Reynolds GP, Cross AJ (1989) Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. J Neurochem 52: 1781–1786PubMedCrossRefGoogle Scholar
  4. Garthwaite G, Garthwaite J (1987) Receptor-linked ionic channels mediate N-methyl-D-aspartate neurotoxicity in rat cerebellar slices. Neurosci Lett 83: 241–246PubMedCrossRefGoogle Scholar
  5. Gibson GE, Peterson C (1987) Calcium and the aging nervous system. Neurobiol Aging 8: 329–343PubMedCrossRefGoogle Scholar
  6. Harrison PJ, McLaughlin D, Kerwin RW (1991) Decreased hippocampal expression of a glutamate receptor gene in schizophrenia. Lancet i: 450–452Google Scholar
  7. Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65: 303–326PubMedCrossRefGoogle Scholar
  8. Kerwin RW, Patel S, Meldrum BS, Czudek C, Reynolds GP (1988) Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia. Lancet i: 583–584Google Scholar
  9. Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20: 379–382PubMedCrossRefGoogle Scholar
  10. Kornhuber J, Mack-Burkhardt F, Riederer P, Hebenstreit GF, Reynolds GP, Andrews HB, Beckmann H (1989) [3H]MK-801 binding sites in postmortem brain regions of schizophrenic patients. J Neural Transm 77: 231–236Google Scholar
  11. Kornhuber J, Riederer P, Beckmann H (1990) The dopaminergic and glutamatergic systems in schizophrenia. In: Bunney WE, Hippius H, Laakmann G, Schmauß M (eds) Neuropsychopharmacology. Springer, Berlin Heidelberg New York Tokyo, pp 714–720CrossRefGoogle Scholar
  12. Kurumaji A, Ishimaru M, Torn M (1990) Quisqualate receptors in post-mortem brain of chronic schizophrenics. Proc Kyoto: New Trends in Schizophrenia and Mood Disorders Research, p 29Google Scholar
  13. Löschmann PA, Lange KW, Kunow M, Rettig KJ, Jähnig P, Honore T, Turski L, Wachtel H, Jenner P, Marsden CD (1991) Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson’s disease. J Neural Transm [PD-Sect] 3: 203–213CrossRefGoogle Scholar
  14. Meldrum B, Garthwaite J (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 11: 379–387PubMedCrossRefGoogle Scholar
  15. Nishikawa T, Takashima M, Torn M (1983) Increased 3H-kainic acid binding in the prefrontal cortex in schizophrenia. Neurosci Lett 40: 245–250PubMedCrossRefGoogle Scholar
  16. Reynolds IR, Miller RJ (1988) Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc. Br J Pharmacol 95: 95–102PubMedGoogle Scholar
  17. Riederer P, Berger W (1991) Locomotion and behaviour: the interaction of loops and transmitter. Proc 5th World Congress of Psychiatry, Florence (in press)Google Scholar
  18. Riederer P, Kornhuber J, Gerlach M, Danielczyk W, Youdim MBH (1991) Glutamatergic-dopaminergic imbalance in Parkinson’s disease and paranoid hallucinatory psychosis. Proc Int Workshop on Parkinson’s Disease, Berlin. Medicom Europe BV (in press)Google Scholar
  19. Schwab RS, England AC, Poskanzer DC, Young RR (1969) Amantadine in the treatment of Parkinson’s disease. J Am Med Assoc 208: 1168CrossRefGoogle Scholar
  20. Sherman AD, Davidson AT, Baruah S, Hegwood TS, Waziri R (1991) Evidence of glutamatergic deficiency in schizophrenia. Neurosci Lett 121: 77–80PubMedCrossRefGoogle Scholar
  21. Suga I, Kobayashi T, Ogata H, Toru M (1990) Increased 3H-MK801 binding sites in post-mortem brains of chronic schizophrenic patients. Proc Kyoto: New Trends in Schizophrenia and Mood Disorders Research, p28Google Scholar
  22. Svensson A, Pileblad E, Carlsson M (1991) A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice. J Neural Transm [Gen Sect] 85: 117–129CrossRefGoogle Scholar
  23. Watkins JC, Kroogsgaard-Larsen P, Honore T (1990) Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci 11: 25–33PubMedCrossRefGoogle Scholar
  24. Weissman AD, Casanova MF, Kleinman JE, London ED, DeSouza EB (1991) Selective loss of cerebral cortical sigma, but not PCP binding sites in schizophrenia. Biol Psychiatry 29: 41–54PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • P. Riederer
    • 1
  • K. W. Lange
    • 1
  • J. Kornhuber
    • 1
  • K. Jellinger
    • 2
  1. 1.Clinical Neurochemistry, Department of PsychiatryUniversity of WürzburgWürzburgFederal Republic of Germany
  2. 2.Ludwig Boltzmann Institute of Clinical NeurobiologyLainz HospitalViennaAustria

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