Analgesic tolerance to microinjection of the μ-opioid agonist DAMGO into the ventrolateral periaqueductal gray

Paul J. Meyer, Erin N. Fossum, Susan L. Ingram, Michael M. Morgan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Repeated administration of the relatively low-efficacy μ-opioid receptor agonist morphine induces tolerance to its antinociceptive effects. High-efficacy agonists such as D-Ala2NMePhe4,Gly-ol5 (DAMGO) have been shown to be less effective at producing tolerance, suggesting that different neural mechanisms underlie tolerance to these agonists. However, the correlation between agonist efficacy and tolerance development has not been examined within the ventrolateral periaqueductal gray (vPAG), a brain area known to be crucial for the development of morphine tolerance. The current studies examined whether tolerance to DAMGO occurs within the vPAG, and whether repeated treatment with DAMGO into the vPAG alters the development of morphine tolerance. The results showed that repeated vPAG microinjections of DAMGO induced robust tolerance and cross-tolerance to morphine. Further, co-administration of a low dose of DAMGO with morphine potentiated morphine tolerance. These findings indicate that similar mechanisms underlie tolerance to morphine and DAMGO within the vPAG.

Original languageEnglish (US)
Pages (from-to)1580-1585
Number of pages6
JournalNeuropharmacology
Volume52
Issue number8
DOIs
StatePublished - Jun 1 2007

Keywords

  • Adaptation
  • Analgesia
  • Antinociception
  • Opiate tolerance
  • Opioid receptor
  • Periaqueductal gray

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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