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Changes in c-fos expression in the rat heart during morphine withdrawal. Involvement of α2-adrenoceptors

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Abstract

We previously demonstrated an increase in Fos expression in the heart during morphine withdrawal. In the present study we examined the role of β- and α-adrenoceptors in naloxone-precipitated increases in Fos expression in the heart. Dependence on morphine was induced by 7-day chronic subcutaneous implantation of six morphine pellets (75 mg). Morphine withdrawal was precipitated by administration of naloxone (5 mg/kg subcutaneously) on day 8. Using immunohistochemical staining of Fos, the present results indicate that morphine withdrawal induced marked Fos immunoreactivity (Fos-IR) within the cardiomyocyte nuclei. Moreover, Western blot analysis revealed a peak expression of c-fos in the right and left ventricles after naloxone-precipitated withdrawal in parallel with an increase in noradrenaline (NA) turnover. In the second study, the effects of the administration of adrenoceptor antagonists on withdrawal-induced Fos expression in the heart were studied. Pretreatment with the β antagonist, propranolol (3 mg/kg intraperitoneally) or α1-adrenoceptor antagonist, prazosin (1 mg/kg intraperitoneally) did not block the marked Fos-IR or the hyperactivity of catecholaminergic neurons observed in the heart during withdrawal. However, pre-treatment with α2-adrenoceptor antagonist, yohimbine (1 mg/kg intraperitoneally), 20 min before naloxone administration to morphine-dependent rats antagonized Fos expression and the enhancement of NA turnover in the heart. Collectively, these results suggest that noradrenergic neurons in the heart are active during morphine withdrawal, and that activation of transcriptional responses mediated by Fos are dependent upon cardiac α2-adrenoceptor.

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Acknowledgments

This work was supported by CICYT(SAF 99–0047; SAF 2002–00763), DGEST (PM99–0140) and Fundación Séneca, Comunidad Autónoma de Murcia (PB 18FS/99; PI-52/00806/FS01).

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Authors and Affiliations

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

    Ana González-Cuello, M. Victoria Milanés & M. Luisa Laorden

  2. Departamento de Farmacología, Facultad de Medicina, 30100, Murcia, Spain

    M. Luisa Laorden

  3. Department of Cell Biology, University School of Medicine, Murcia, Spain

    Manuel Aviles

Authors
  1. Ana González-Cuello
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  2. M. Victoria Milanés
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  3. Manuel Aviles
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  4. M. Luisa Laorden
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Correspondence to M. Luisa Laorden.

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González-Cuello, A., Milanés, M.V., Aviles, M. et al. Changes in c-fos expression in the rat heart during morphine withdrawal. Involvement of α2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 370, 17–25 (2004). https://doi.org/10.1007/s00210-004-0946-1

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  • DOI: https://doi.org/10.1007/s00210-004-0946-1

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