Continued morphine modulation of calcium channel currents in acutely isolated locus coeruleus neurons from morphine-dependent rats

Mark Connor*, Stephanie L. Borgland, Macdonald J. Christie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

1. The actions of the opioid agonists morphine and methionine-enkephalin (met-enkephalin) on the calcium channel currents (I(Ba)) of acutely isolated locus coeruleus (LC neurons from morphine-dependent and vehicle-treated rats were examined using whole cell patch clamp techniques. 2. In LC neurons maintained in 5 μM morphine, co-superfusion of naloxone (1 μM) or the μ-opioid receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 1 μM) with morphine resulted in a significant increase in the amplitude of I(Ba). The increases in I(Ba) were not different in neurons from morphine-dependent or vehicle rats. The increase in I(Ba) was mimicked by washing off morphine, but not by co-superfusion of the κ-receptor antagonist norbinaltorphimine (300 nM) or the δ-receptor antagonist ICI-174864 (1 μM). 3. In spontaneously withdrawn LC neurons from morphine-dependent rats, met-enkephalin (pD2 7.1, maximum inhibition 49%) and morphine (pD2 6.5, maximum inhibition 33%) inhibited I(Ba) in all cells. In cells from vehicle rats the pD2 for met-enkephalin was 7.3, maximum inhibition 52% while the pD2 for morphine was 6.6 and the maximum inhibition 43% (P < 0.05 versus cells from morphine-dependent rats). 4. I(Ba) in LC neurons was mostly comprised of ω-conotoxin GVIA- (N-type) and ω-agatoxin IVA-(P/Q-type) sensitive components, with lesser amounts of nimodipine-sensitive current and current resistant to all three blockers. Neither the density of I(Ba) nor the proportion of any of the components of I(Ba) differed between neurons from morphine-dependent or vehicle-treated rats. 5. This study demonstrates that in morphine-dependent rats, morphine and met-enkephalin modulation of somatic I(Ba) in LC neurons displays modest tolerance compared with untreated rats. Further, chronic morphine treatment does not alter the type or density of I(Ba) in LC neurons. These results provide more evidence that functional μ-opioid receptor coupling is not dramatically altered in the LC in morphine-dependent rats.

Original languageEnglish
Pages (from-to)1561-1569
Number of pages9
JournalBritish Journal of Pharmacology
Volume128
Issue number7
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Calcium channels
  • Locus coeruleus
  • Met-enkephalin
  • Morphine
  • Opioid dependence
  • Opioid tolerance
  • Withdrawal

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