Site-selective acute desensitization following local administration of opioid in the hippocampus

Site-selective acute desensitization following local administration of opioid in the hippocampus Electrophoretic administration of the μ selective opioid agonist (D-Ala 2 , NMe-Phe 4 , Gly-ol)-Enkephalin (DAMGO) in the dentate gyrus of the hippocampus acutely produces a marked increase in the responsiveness of dentate granule cells to perforant path stimulation. This can be measured by an increase in the primary population spike (PS) amplitude and by disinhibition in the paired-pulse (PP) paradigm. Concomitantly, the spontaneous single unit activity of interneurons is usually inhibited. We have observed that after prolonged (usually 10–20 min) local (electrophoretic) administration of DAMGO, a second, late effect is noted, suggesting acute desensitization. There is a loss of the disinhibition seen in the PP paradigm while the primary PS shows only some increased variability in response to stimulation. Furthermore, in a time course parallel to the loss of disinhibition, single cell activity intially inhibited by DAMGO appears to lose its responsiveness. Pretreatment with κ or δ opioid agonists, or with GABA agonists and antagonists, does not affect the development of this desensitization suggesting selective involvement of the μ receptor. We further propose a regional specificity within the hippocampus since we are unable to detect evidence of desensitization to opioid in CA1 using the same techniques. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Site-selective acute desensitization following local administration of opioid in the hippocampus

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Science B.V. All rights reserved
ISSN
0006-8993
DOI
10.1016/0006-8993(95)00444-U
Publisher site
See Article on Publisher Site

Abstract

Electrophoretic administration of the μ selective opioid agonist (D-Ala 2 , NMe-Phe 4 , Gly-ol)-Enkephalin (DAMGO) in the dentate gyrus of the hippocampus acutely produces a marked increase in the responsiveness of dentate granule cells to perforant path stimulation. This can be measured by an increase in the primary population spike (PS) amplitude and by disinhibition in the paired-pulse (PP) paradigm. Concomitantly, the spontaneous single unit activity of interneurons is usually inhibited. We have observed that after prolonged (usually 10–20 min) local (electrophoretic) administration of DAMGO, a second, late effect is noted, suggesting acute desensitization. There is a loss of the disinhibition seen in the PP paradigm while the primary PS shows only some increased variability in response to stimulation. Furthermore, in a time course parallel to the loss of disinhibition, single cell activity intially inhibited by DAMGO appears to lose its responsiveness. Pretreatment with κ or δ opioid agonists, or with GABA agonists and antagonists, does not affect the development of this desensitization suggesting selective involvement of the μ receptor. We further propose a regional specificity within the hippocampus since we are unable to detect evidence of desensitization to opioid in CA1 using the same techniques.

Journal

Brain ResearchElsevier

Published: Jul 24, 1995

References

  • A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices
    Chavez-Noriega, L.E.; Halliwell, J.V.; Bliss, T.V.P.
  • Role of receptor regulation in opioid tolerance mechanisms
    Loh, H.H.; Tao, P.L.; Smith, A.P.
  • Differential effects of mu-and delta-receptor selective opioid agonists on feedforward and feedback GABAergic inhibition in hippocampal brain slices
    Lupica, C.R.; Dunwiddie, T.V.
  • Enkephalin hyperpolarizes interneurones in the rat hippocampus
    Madison, D.V.; Nicoll, R.A.
  • Mu opioid receptor-mediated modulation of synaptic currents in dentate granule cells of rat hippocampus
    Xie, C.W.; Morrisett, R.A.; Lewis, D.V.

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