Pre- and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment

A study of GIRK-knockout mice

Maria Torrecilla, Nidia Quillinan, John Williams, Kevin Wickman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

While the acute inhibitory effect of opioids on locus coeruleus (LC) neurons is mediated primarily by the activation of G protein-gated inwardly-rectifying K+ (GIRK) channels, the 3′-5′-cyclic adenosine monophosphate (cAMP) system has been implicated in the effects of chronic morphine exposure. Presently, the impact of chronic morphine treatment on GIRK-dependent and GIRK-independent mechanisms underlying the opioid-induced inhibition of LC neurons is unclear. Here, opioid-induced postsynaptic inhibition was studied in LC neurons from wild-type and GIRK2/GIRK3 -/- mice at baseline and following chronic morphine treatment. The postsynaptic inhibition of LC neurons caused by the opioid agonist [Met] 5 enkephalin (ME) was unaffected by chronic morphine treatment in mice of either genotype. Furthermore, chronic morphine treatment had no effect on the forskolin augmentation of the ME-induced current in wild-type LC neurons and only a minor effect on the ME-induced current in LC neurons from GIRK2/GIRK3-/- mice. Chronic morphine treatment did, however, lead to an increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the LC. Interestingly, while forskolin augmented the EPSC frequency similarly in untreated and morphine-treated wild-type mice, as well as untreated GIRK2/GIRK3-/- mice, it failed to increase the frequency of EPSCs in morphine-treated GIRK2/GIRK3-/- mice. Altogether, the findings suggest that chronic morphine treatment exerts little impact on ion channels and signaling pathways that mediate the postsynaptic inhibitory effects of opioids but does enhance excitatory neurotransmission in the mouse LC.

Original languageEnglish (US)
Pages (from-to)618-624
Number of pages7
JournalEuropean Journal of Neuroscience
Volume28
Issue number3
DOIs
StatePublished - Aug 2008

Fingerprint

Locus Coeruleus
Knockout Mice
Morphine
Neurons
Opioid Analgesics
Methionine Enkephalin
Excitatory Postsynaptic Potentials
Colforsin
Inwardly Rectifying Potassium Channel
Ion Channels
GTP-Binding Proteins
Synaptic Transmission
Cyclic AMP
Genotype

Keywords

  • Dependence
  • Kir3
  • Opioid
  • Tolerance
  • Withdrawal

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pre- and postsynaptic regulation of locus coeruleus neurons after chronic morphine treatment : A study of GIRK-knockout mice. / Torrecilla, Maria; Quillinan, Nidia; Williams, John; Wickman, Kevin.

In: European Journal of Neuroscience, Vol. 28, No. 3, 08.2008, p. 618-624.

Research output: Contribution to journalArticle

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