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

Nature volume 363, pages 451–454 (1993)Cite this article

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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Author information

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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