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Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5

Abstract

Recent work has shown that the hippocampus contains a class of receptors for the excitatory amino acid glutamate that are activated by N-methyl-D-aspartate (NMDA)1 and that exhibit a peculiar dependency on membrane voltage in becoming active only on depolarization2,3. Blockade of these sites with the drug aminophosphonovaleric acid (AP5) does not detectably affect synaptic transmission in the hippocampus, but prevents the induction of hippocampal long-term potentiation (LTP) following brief high-frequency stimulation4–6. We now report that chronic intraventricular infusion of D, L-AP5 causes a selective impairment of place learning, which is highly sensitive to hippocampal damage7, without affecting visual discrimination learning, which is not8. The L-isomer of AP5 did not produce behavioural effects. AP5 treatment also suppressed LTP in vivo. These results suggest that NMDA receptors are involved in spatial learning, and add support to the hypothesis9–11 that LTP is involved in some, but not all, forms of learning.

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References

  1. Watkins, J. C. & Evans, R. H. A. Rev. Pharmac. Tox. 21, 165–204 (1981).

    Article  CAS  Google Scholar 

  2. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Nature 307, 462–465 (1984).

    Article  ADS  CAS  Google Scholar 

  3. Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Nature 309, 261–263 (1984).

    Article  ADS  CAS  Google Scholar 

  4. Bliss, T. V. P. & Lomo, T. J. Physiol., Lond. 232, 331–356 (1973).

    Article  CAS  Google Scholar 

  5. Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol., Lond. 334, 19–31 (1983).

    Article  CAS  Google Scholar 

  6. Harris, E. W., Ganong, A. H. & Cotman, C. W. Brain Res. 323, 132–137 (1984).

    Article  CAS  Google Scholar 

  7. Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O'Keefe, J. Nature 297, 681–683 (1982).

    Article  ADS  CAS  Google Scholar 

  8. O'Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Oxford University Press, 1978).

    Google Scholar 

  9. Andersen, P. Prog. Brain Res. 58, 419–426 (1983).

    Article  CAS  Google Scholar 

  10. McNaughton, B. L. in Neurobiology of the Hippocampus (ed. Siefert, W.) (Academic, London, 1983).

    Google Scholar 

  11. Lynch, G. & Baudry, M. Science 224, 1057–1063 (1984).

    Article  ADS  CAS  Google Scholar 

  12. Morris, R. G. M. J. Neurosci. Meth. 11, 47–60 (1984).

    Article  CAS  Google Scholar 

  13. Sutherland, R. J., Whishaw, I. Q. & Kolb, B. Behavioural Brain Res. 7, 133–153 (1983).

    Article  CAS  Google Scholar 

  14. Kolb, B., Pittman, K. & Sutherland, R. J. Behav. Brain Res. (in the press).

  15. Kolb, B., Sutherland, R. J. & Whishaw, I. Q. Behav. Neurosci. 97, 13–27 (1983).

    Article  CAS  Google Scholar 

  16. Hagan, J.J., Alpert, J. E., Morris, R. G. M. & Iversen, S. D. Behav. Brain Res. 9, 83–104 (1983).

    Article  CAS  Google Scholar 

  17. Hagan, J. J., Tweedie, F. M. & Morris, R. G. M. Behav. Neurosci. (in the press).

  18. Barnes, C. A. & McNaughton, B. L. Soc. Neurosci. Abstr. 9, 191.16 (1983).

  19. Croucher, M. J., Collins, J. F. & Meldrum, B. S. Science 216, 899–901 (1982).

    Article  ADS  CAS  Google Scholar 

  20. Meldrum, B. S. Clin. Sci. 68, 113–122 (1985).

    Article  CAS  Google Scholar 

Download references

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Morris, R., Anderson, E., Lynch, G. et al. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–776 (1986). https://doi.org/10.1038/319774a0

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