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Morphine withdrawal-induced c-fos expression in the heart: a peripheral mechanism

Ana González-Cuello1, M Victoria Milanés, M Teresa Castells

  • 1Department of Cellular and Molecular Pharmacology, University School of Medicine, Murcia, Spain.

European Journal of Pharmacology
|March 23, 2004
PubMed

Insights

Morphine withdrawal activates cardiac cells via peripheral mechanisms, not the central nervous system. This study shows naloxone methiodide and naloxone trigger Fos expression in heart cells during withdrawal.

Area of Science:

  • Neuroscience
  • Cardiology
  • Pharmacology

Background:

  • Morphine withdrawal causes cardiac noradrenergic hyperactivity.
  • Previous research indicated peripheral mechanisms mediate this hyperactivity.

Purpose of the Study:

  • To investigate the role of peripheral mechanisms in morphine withdrawal-induced cardiac hyperactivity.
  • To differentiate between central nervous system (CNS) and peripheral effects on cardiac c-fos expression during withdrawal.

Main Methods:

  • Morphine dependence was induced in rats via subcutaneous pellets.
  • Withdrawal was precipitated using naloxone methiodide (peripheral) or naloxone (central/peripheral).
  • Fos immunostaining and Western blot analysis were used to assess neuronal and cellular activity in the heart and hypothalamus.

Main Results:

  • Both naloxone methiodide and naloxone induced significant Fos immunoreactivity in cardiomyocyte nuclei.
  • Peak c-fos expression was observed in ventricles during precipitated withdrawal.
  • Naloxone, but not naloxone methiodide, increased Fos expression in the hypothalamic paraventricular nucleus (PVN).

Conclusions:

  • Cardiac c-fos expression during morphine withdrawal is primarily mediated by intrinsic cardiac mechanisms, independent of the CNS.
  • Peripheral pathways play a crucial role in the cardiac response to morphine withdrawal.

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