Contribution of supraspinal mu- and delta-opioid receptors to antinociception in the rat

Eur J Pharmacol. 1991 Dec 3;205(3):247-52. doi: 10.1016/0014-2999(91)90905-6.


This study evaluated the contribution of supraspinal opioid receptors to the production of antinociception, in the rat. I.c.v. administration of a selective mu- (DAMGO) and a selective delta- (DPDPE), but not a selective kappa- (U50,488H) opioid receptor agonist, produced significant dose-dependent increase in mechanical nociceptive thresholds. ICI 174,864, a delta-opioid receptor antagonist, completely blocked the antinociceptive effects produced by DPDPE ([D-Pen2,D-Pen5]enkephalin) at a dose that had no effect on the increases in nociceptive thresholds produced by DAMGO ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin). The simultaneous i.c.v. administration of a low-antinociceptive dose of DAMGO or DPDPE given in combination with sequentially increasing doses of the other opioid agonist, produced synergy (i.e., a more than additive antinociceptive effect), at the lower doses tested. The results of these experiments provide evidence to support the suggestion that both supraspinal mu- and delta-opioid receptors contribute to the production of antinociception, in the rat.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalin, Leucine / analogs & derivatives
  • Enkephalin, Leucine / pharmacology
  • Enkephalins / pharmacology
  • Injections, Intraventricular
  • Male
  • Narcotic Antagonists / pharmacology
  • Nociceptors / physiology*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Spinal Cord / physiology
  • Spinal Cord / ultrastructure*


  • Analgesics
  • Enkephalins
  • Narcotic Antagonists
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, Leucine
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Enkephalin, D-Penicillamine (2,5)-
  • N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine