Antisense oligodeoxynucleotides to the kappa-1 receptor block the antinociceptive effects of delta 9-THC in the spinal cord

Brain Res. 1995 Aug 14;689(1):157-8. doi: 10.1016/0006-8993(95)00560-d.

Abstract

Intrathecal pretreatment of mice with an antisense oligodeoxynucleotide directed against the kappa-1 receptor significantly reduced the antinociceptive effects of the kappa receptor agonist U50,488 as well as delta 9-THC, the major psychoactive ingredient found in cannabis. A mismatched oligodeoxynucleotide which contained four switched bases did not block the antinociception produced by U50,488 or delta 9-THC. Furthermore, kappa-1 antisense did not alter the antinociceptive effects of either the mu receptor-selective opioid DAMGO, or the delta receptor-selective opioid DPDPE. By using kappa-1 antisense, we were able to demonstrate that an interaction occurs between the cannabinoids and opioids in the spinal cord.

Publication types

  • 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 / antagonists & inhibitors*
  • Animals
  • Base Sequence
  • Dronabinol / antagonists & inhibitors*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology*
  • Pain / physiopathology*
  • Psychotropic Drugs / antagonists & inhibitors*
  • Pyrrolidines / antagonists & inhibitors
  • Receptors, Opioid, kappa / drug effects*
  • Spinal Cord / drug effects*

Substances

  • Analgesics
  • Enkephalins
  • Oligonucleotides, Antisense
  • Psychotropic Drugs
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Dronabinol
  • Enkephalin, D-Penicillamine (2,5)-