Opioid desensitization: Interactions with G-protein-coupled receptors in the locus coeruleus

Christopher D. Fiorillo, John T. Williams

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


In rat locus coeruleus (LC) neurons, α2 adrenoceptors, μ-opioid and somatostatin receptors all activate the same potassium conductance. Chronic treatment with morphine causes a loss of sensitivity that is specific to the μ-opioid response, with no change in the α2 adrenoceptor-mediated response. Acute desensitization induced by opioid, somatostatin, and α2- adrenoceptor agonists was studied in brain slices of rat LC using intracellular recording. A supramaximal concentration of the opioid agonist Met5-enkephalin induced a profound homologous desensitization but little heterologous desensitization to an α2-adrenoceptor agonist (UK 14304) or somatostatin. All desensitized currents showed partial recovery. A supramaximal concentration of UK14304 caused a relatively small amount of desensitization. Although little interaction was observed among inhibitory G- protein-coupled receptors, activation of an excitatory receptor had marked effects on inhibitory responses. Muscarinic agonists, which produce an inward current in LC neurons, reduced the magnitude of agonist-induced outward currents and increased both the rate and amount of opioid desensitization. Muscarinic activation did not alter desensitization of α2-adrenoceptor responses. Acute desensitization shares several characteristics with the tolerance induced by chronic morphine treatment of animals.

Original languageEnglish (US)
Pages (from-to)1479-1485
Number of pages7
JournalJournal of Neuroscience
Issue number4
StatePublished - Feb 15 1996


  • brain slices
  • desensitization
  • locus coeruleus
  • muscarinic
  • somatostatin
  • α adrenoceptor
  • μ-opioid

ASJC Scopus subject areas

  • Neuroscience(all)


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