An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice

Benjamin Kest, Cynthia E. Lee, Gabrielle L. McLemore, Charles E. Inturrisi

Research output: Contribution to journalArticle

Abstract

Pharmacological data from several laboratories support a modulatory role for the delta opioid receptor in morphine analgesia, tolerance, and physical dependence. We examined the role of the delta opioid receptor in these processes using an in vivo antisense strategy in mice. Intracerebroventricular administration of a 20mer antisense or a mismatch control oligodeoxynucleotide (ODN) targeting the mRNA of the cloned delta opioid receptor (DOR-1) for 3 days did not affect baseline nociceptive thresholds or morphine analgesia compared to untreated or saline-treated mice. However, dose-response studies indicate that the induction of morphine tolerance following 3 days of chronic morphine administration was blocked in antisense but not mismatch ODN or saline-treated mice. Antisense ODN treatment also blocked the development of acute morphine dependence, whereas similar protection was not afforded to mice treated with saline or mismatch ODN. This study demonstrates the relevance of the cloned DOR-1 in morphine tolerance and dependence and provides new evidence for a modulatory role of the delta opioid receptor using this novel approach.

Original languageEnglish (US)
Pages (from-to)185-188
Number of pages4
JournalBrain Research Bulletin
Volume39
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Delta opioid receptor
  • Morphine analgesia
  • Physical dependence
  • Tolerance

ASJC Scopus subject areas

  • Neuroscience(all)

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