Abstract
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*
Substances
-
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