Desensitization and tolerance of Mu opioid receptors on pontine kölliker-fuse neurons

Erica S. Levitt, John T. Williams

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein–coupled inwardly rectifying potassium current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices. A saturating concentration of the opioid agonist [Met5]-enkephalin (ME) caused significantly less desensitization in KF neurons compared with LC neurons. In contrast to LC, desensitization in KF neurons was not enhanced by activation of protein kinase C or in slices from morphine-treated rats. Cellular tolerance to ME and morphine was also lacking in KF neurons from morphine-treated rats. The lack of cellular tolerance in KF neurons correlates with the relative lack of tolerance to the respiratory depressant effect of opioids.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalMolecular pharmacology
Volume93
Issue number1
DOIs
StatePublished - Jan 2018

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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