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Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus

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Abstract

ALTHOUGH anatomical and neurochemical studies suggest that endogenous opioids act as neurotransmitters1–7, their roles in normal and pathophysiological regulation of synaptic transmission are not defined. Here we examine the actions of prodynorphin-derived opioid peptides in the guinea-pig hippocampus and show that physiological stimulation of the dynorphin-containing dentate granule cells can release endogenous dynorphins, which then activate κ1 opioid receptors present in the molecular layer of the dentate gyrus. Activation of κ1 receptors by either pharmacologically applied agonist or endogenously released peptide reduces excitatory transmission in the dentate gyrus, as shown by a reduction in the excitatory postsynaptic currents evoked by stimulation of the perforant path, a principal excitatory afferent. In addition, released dynorphin peptides were found to block the induction of long-term potentiation (LTP) at the granule cell-perforant path synapse. The results indicate that endogenous dynorphins function in this hippocampal circuit as retrograde, inhibitory neurotransmitters.

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References

  1. Gall, C., Brecha, N., Karten, H. J. & Chang, K. J. comp. Neurol. 198, 335–350 (1981).

    Article  CAS  Google Scholar 

  2. McGinty, J. F., Henriksen, S. J., Goldstein, A., Terenius, L. & Bloom, F. E. Proc. natn. Acad. Sci. U.S.A. 80, 589–593 (1983).

    Article  ADS  CAS  Google Scholar 

  3. Chavkin, C., Shoemaker, W. J., McGinty, J. F., Bayon, A. & Bloom, F. E. J. Neurosci. 5, 808–816 (1985).

    Article  CAS  Google Scholar 

  4. McLean, S., Rothman, R., Jacobson, A., Rice, K. & Herkenham, M. J. comp. Neurol. 255, 497–510 (1987).

    Article  CAS  Google Scholar 

  5. Chavkin, C., Bakhit, C., Weber, E. & Bloom, F. E. Proc. natn. Acad Sci. U.S.A. 80, 7669–7673 (1983).

    Article  ADS  CAS  Google Scholar 

  6. Wagner, J. J., Evans, C. & Chavkin, C. J. Neurochem. 57, 333–343 (1991).

    Article  CAS  Google Scholar 

  7. Wagner, J. J., Caudle, R. M. & Chavkin, C. J. Neurosci. 12, 132–141 (1992).

    Article  CAS  Google Scholar 

  8. Lahti, R., Mickelson, M., McCall, J. & von Voightlander, P. Eur. J. Pharmac. 109, 281 (1985).

    Article  CAS  Google Scholar 

  9. Zukin, R., Eghbali, M., Olive, D., Unterwald, E. & Tempel, A. Proc. natn. Acad. Sci. U.S.A. 85, 4061–4065 (1988).

    Article  ADS  CAS  Google Scholar 

  10. Portoghese, P. S., Lipkowski, A. W. & Takemori, A. E. Life Sci. 40, 1287–1292 (1987).

    Article  CAS  Google Scholar 

  11. Nock, B., Giordano, L., Cicero, T. & O'Connor, L. J. Pharmac. exp. Ther. 254, 412–419 (1990).

    CAS  Google Scholar 

  12. Jan, L. Y. & Jan, Y. N. J. Physiol., London 327, 219–246 (1982).

    Article  CAS  Google Scholar 

  13. Lundberg, J. M., Rudehill, A., Sollevi, A., Theodorsson-Norheim, E. & Hamberger, B. Neurosci. Lett. 63, 96–100 (1986).

    Article  CAS  Google Scholar 

  14. Bliss, T. V. P. & Lomo, T. J. Physiol. 232, 331 (1973).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  16. Madison, D. V., Malenka, R. C. & Nicoll, R. A. Rev. Neurosci. 14, 379–397 (1991).

    Article  CAS  Google Scholar 

  17. Martinez, J. L., Janak, P. H., Weinberger, S. G., Schulties, G. & Derrick, R. E. in NIDA Res. Monogr. 97 (ed. Erinoff, L.) 48–78 (US Govt Printing Office, Washington DC, 1990).

    Google Scholar 

  18. Decker, M. W. & McGaugh, J. L. Synapse 7, 151–168 (1991).

    Article  CAS  Google Scholar 

  19. Jiang, H. K., Owyang, V., Hang, J. S. & Gallagher, M. Proc. natn. Acad. Sci. U.S.A. 86, 2948–2951 (1989).

    Article  ADS  CAS  Google Scholar 

  20. Gallagher, M., Bostock, E. & King, R. A. Behavl Neural Biol. 44, 374–385 (1985).

    Article  CAS  Google Scholar 

  21. Collier, T. J. & Routtenberg, A. Brain Res. 310, 384–387 (1984).

    Article  CAS  Google Scholar 

  22. Bramham, C., Milgram, N. & Srebo, B. Brain Res. 567, 42–50 (1991).

    Article  CAS  Google Scholar 

  23. Xie, C. W. & Lewis, D. V. J. Pharmac. exp. Ther. 256, 289–296 (1991).

    CAS  Google Scholar 

  24. Tortella, F. C. Trends pharmac. Sci. 9, 366–372 (1988).

    Article  CAS  Google Scholar 

  25. Singh, L., Vass, C. A., Hunter, J. C., Woodruff, G. N. & Hughes, J. Eur. J. Pharmac. 191, 477–480 (1990).

    Article  CAS  Google Scholar 

  26. Jones, L. S. Brain Res. 564, 336–340 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Houser, C. R., Miyashiro, J. E., Walsh, G. O., Rich, J. R. & Delgado-Escueta, A. V. J. Neurosci. 10, 267–282 (1990).

    Article  CAS  Google Scholar 

  28. Sloviter, R. S. Neurosci. Lett. 137, 91–96 (1992).

    Article  CAS  Google Scholar 

  29. Cronin, J., Obenaus, A., Houser, C. R. & Dudek, F. E. Brain Res. 573, 305–310 (1992).

    Article  CAS  Google Scholar 

  30. Evans, C., Erdelyi, E., Hunter, J. & Barchas, J. J. Neurosci. 5, 3423–3427 (1985).

    Article  CAS  Google Scholar 

  31. Weisskopf, M. G., Zalutsky, R. A. & Nicoll, R. A. Nature 362, 423–427 (1993).

    Article  ADS  CAS  Google Scholar 

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Author notes

  1. John J. Wagner

    Present address: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

  2. Charles Chavkin: To whom correspondence should be addressed.

Authors and Affiliations

  1. Departments of Pharmacology, University of Washington, Seattle, Washington, 98195, USA

    Gregory W. Terman

  2. Departments of Anesthesiology, SJ-30, University of Washington, Seattle, Washington, 98195, USA

    Gregory W. Terman

Authors
  1. John J. Wagner
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  2. Gregory W. Terman
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  3. Charles Chavkin
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Wagner, J., Terman, G. & Chavkin, C. Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature 363, 451–454 (1993). https://doi.org/10.1038/363451a0

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