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Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis

Abstract

The movement disorder tardive dyskinesia is a serious side effect of the long-term treatment of schizophrenia with neuroleptic drugs. Similar symptoms to those of tardive dyskinesia have been observed in Cebus apella monkeys following long-term treatment with neuroleptic drugs1,2, and these monkeys may therefore be a useful animal model of tardive dyskinesia. Motor defects have persisted in these dyskinetic monkeys for periods of 1–6 yr after the cessation of neuroleptic treatment. We report here that in three regions of the brains of dyskinetic monkeys (substantia nigra, medial globus pallidus and subthalamic nucleus) glutamate decarboxylase activities and γ-aminobutyric acid (GABA) levels are reduced relative to control monkeys that had been treated with neuroleptics but which showed none of the symptoms of tardive dyskinesia. These results suggest that alterations in the GABA neurone system are involved in neuroleptic drug-induced tardive dyskinesia.

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References

  1. Gunne, L.-M. & Bárány, S. Psychopharmacology 50, 237–240 (1976).

    Article  CAS  Google Scholar 

  2. Bárány, S., Ingvast, A. & Gunne, L.-M. Res. Commun. chem. Path. Pharmac. 25, 269–279 (1979).

    Google Scholar 

  3. Bárány, S. A Primate Model for Acute Dystonia and Tardive Dyskinesia (Almqvist & Wiksell, Stockholm, 1983).

    Google Scholar 

  4. Gunne, L.-M. & Häggström, J.-E. Psychopharmacology 81, 191–194 (1983).

    Article  CAS  Google Scholar 

  5. Häggström, J.-E., Sjöquist, B., Eckernäs, S.-Å, Ingvast, A. & Gunne, L.-M. Acta physiol. scand. suppl. (in the press).

  6. Wiesel, F. A. & Sedvall, G. Brain Res. 65, 547–550 (1974).

    Article  CAS  Google Scholar 

  7. Gale, K. & Casu, M. Molec. cell. Biochem. 39, 369–405 (1981).

    Article  CAS  Google Scholar 

  8. Mao, C. & Costa, E. Psychopharmacology: A Generation of Progress (eds Lipton, M. A., DiMasicio, A. & Killam, K. F.) 307–318 (Raven, New York, 1978).

    Google Scholar 

  9. Redgrave, P., Dean, P., Souki, W. & Lewis, G. Psychopharmacology 75, 198–205 (1981).

    Article  CAS  Google Scholar 

  10. Childs, J. A. & Gale, K. Life Sci. 33, 1007–1010 (1983).

    Article  CAS  Google Scholar 

  11. Kilpatrick, I. C., Starr, M. S., James, T. A. & MacLeod, M. K. in GABA and the Basal Ganglia (eds DiChiara, G. & Gessa, G. L.) 205–224 (Raven, New York, 1981).

    Google Scholar 

  12. Reavill, C., Leigh, N., Jenner, P. & Marsden, C. D. Nature 287, 368 (1980).

    Article  ADS  CAS  Google Scholar 

  13. Arnt, J. & Scheel-Krüger, J. Eur. J. Pharmac. 62, 51–61 (1980).

    Article  CAS  Google Scholar 

  14. Coyle, J. T., Schwarcz, R., Bennet, J. P. & Campochiaro, P. Prog. Neuro-psychopharmac, 1, 13–20 (1977).

    Article  CAS  Google Scholar 

  15. McGeer, P. L. & McGeer, E. G. J. Neurochem. 26, 65–76 (1976).

    CAS  PubMed  Google Scholar 

  16. Lloyd, K. G. & Hornykiewicz, O. Nature 243, 522–523 (1973).

    Article  ADS  Google Scholar 

  17. Brown, L. L. & Wolfson, L. I. Brain Res. 261, 213–229 (1983).

    Article  ADS  CAS  Google Scholar 

  18. Ribak, C. E. in GABA and the Basal Ganglia (eds DiChiara, G. & Gessa, G. L.) 23–36 (Raven, New York, 1981).

    Google Scholar 

  19. Kim, J. S., Bak, I. J., Hassler, R. & Okada, Y. Expl Brain Res. 14, 95–104 (1971).

    Article  CAS  Google Scholar 

  20. Hattori, T., McGeer, P. L., Fibiger, H. & McGeer, E. G. Brain Res. 54, 103–114 (1973).

    Article  CAS  Google Scholar 

  21. Andén, N.-E. & Stock, G. Naunyn-Schmiedebergs Archs Pharmak. 279, 89–92 (1973).

    Article  Google Scholar 

  22. Bartholini, G. & Stadler, H. in Chemical Tools in Catecholamine Research Vol 2 (eds Almgren, O., Carlsson, A. & Engel, J.) 235–241 (North-Holland, Amsterdam, 1975).

    Google Scholar 

  23. Hornykiewicz, O., Lloyd, K. G. & Davidson, L. in GABA in Nervous System Function (eds Roberts, E., Chase, T. N. & Tower, D. B.) 479–485 (Raven, New York, 1976).

    Google Scholar 

  24. Groves, P. M., Wilson, C. J., Young, S. J. & Rebec, G. V. Science 190, 522–529 (1975).

    Article  ADS  CAS  Google Scholar 

  25. Scheel-Krüger, J., Arnt, J., Braestrup, C., Christensen, A. V. & Magelund, G. in GABA-Neurotransmitters (eds Krogsgaard-Larsen, P., Scheel-Krüger, J. & Kofod, H.) 447–464 (Munksgaard, Copenhagen and Academic, New York, 1978).

    Google Scholar 

  26. Grace, A. A. & Bunney, B. S. Eur. J. Pharmac. 59, 211–218 (1979).

    Article  CAS  Google Scholar 

  27. Martin, G. E. & Haubrich, D. R. Nature 275, 230–231 (1978).

    Article  ADS  CAS  Google Scholar 

  28. Waszcak, B. L., Eng, N. & Walters, J. R. Brain Res. 188, 185–197 (1980).

    Article  Google Scholar 

  29. Klawans, H. L. Jr. Am. J. Psychiat. 130, 82–86 (1973).

    Article  Google Scholar 

  30. Tarsy, D. & Baldessarini, R. J. Biol. Psychiat. 12, 431–450 (1977).

    CAS  PubMed  Google Scholar 

  31. Asper, H. et al. Eur. J. Pharmac. 22, 287–294 (1973).

    Article  CAS  Google Scholar 

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Gunne, LM., Häggström, JE. & Sjöquist, B. Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. Nature 309, 347–349 (1984). https://doi.org/10.1038/309347a0

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