Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor

Life Sci. 1994;54(21):PL375-9. doi: 10.1016/0024-3205(94)90038-8.

Abstract

The recent cloning of mu, delta and kappa 1 opioid receptors has provide opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa 1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions.

Publication types

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

MeSH terms

  • Analgesia*
  • Animals
  • Base Sequence
  • Male
  • Microinjections
  • Molecular Sequence Data
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacology*
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / genetics*

Substances

  • Oligonucleotides, Antisense
  • Receptors, Opioid, mu
  • Morphine