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Role of PKC in regulation of Fos and TH expression after naloxone induced morphine withdrawal in the heart

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Abstract

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. The present study was designed to investigate the role of protein kinase C (PKC) in this process, by estimating whether pharmacological inhibition of PKC would attenuate morphine withdrawal induced Fos expression and changes in tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced on day 8 by an injection of naloxone. Morphine withdrawal induced Fos expression and increased TH levels and NA turnover in the right and left ventricle. Infusion of calphostin C, a selective PKC inhibitor, did not modify the morphine withdrawal-induced increase in NA turnover and TH levels. However, this inhibitor produced a reduction in the morphine withdrawal-induced Fos expression. The results of the present study provide new information on the mechanisms that underlie morphine withdrawal-induced up-regulation of Fos expression in the heart and suggest that TH is not a target of PKC during morphine withdrawal at heart levels.

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Acknowledgements

This work was supported by Ministerio de Ciencia y Tecnología (SAF/FEDER 2002–00763, 2003–00756) and Ministerio del Interior, Madrid Spain.

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Authors and Affiliations

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

    Pilar Almela, Manuela Cerezo, M. Victoria Milanés & M. Luisa Laorden

  2. Department of Pharmacology, University School of Medicine, Campus de Espinardo, 30100, Murcia, Spain

    M. Luisa Laorden

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  1. Pilar Almela
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  2. Manuela Cerezo
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  4. M. Luisa Laorden
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Correspondence to M. Luisa Laorden.

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Almela, P., Cerezo, M., Milanés, M.V. et al. Role of PKC in regulation of Fos and TH expression after naloxone induced morphine withdrawal in the heart. Naunyn Schmied Arch Pharmacol 372, 374–382 (2006). https://doi.org/10.1007/s00210-006-0032-y

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  • DOI: https://doi.org/10.1007/s00210-006-0032-y

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