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The Role of Mitogen-Activated Protein Kinase (MAPK) in Morphine Tolerance and Dependence

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Abstract

Despite the existence of a large body of information on the subject, the mechanisms of morphine tolerance and dependence are not yet fully understood. There is substantial evidence indicating that mitogen-activated protein kinase (MAPK), a family including extracellular signal-regulated protein kinase, p38 MAPK, and c-Jun N-terminal kinase, can be activated by chronic morphine treatment in the central and peripheral nervous systems and that application of a MAPK inhibitor reduces morphine tolerance and dependence. While the exact mechanism is not completely understood, recent evidence suggests that the activation of MAPK induced by long-term morphine exposure may participate in tolerance and dependence by regulating the downstream targets, such as calcitonin gene-related peptide, substance P, nitric oxide, transient receptor potential vanilloid 1, and proinflammatory cytokines. In this review, we focus on the current understanding of the role of MAPK signaling pathways in morphine tolerance and dependence.

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Acknowledgements

The authors of the manuscript declare that there are no conflicts of interest with this review. The work was supported by research funds from the University of Würzburg.

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  1. Center for Translational Neuroscience, Duke University, Durham, NC, 27710, USA

    Yong Chen

  2. Department of Neurology, University of Würzburg, Würzburg, 97080, Germany

    Claudia Sommer

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  1. Yong Chen
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Correspondence to Yong Chen.

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Chen, Y., Sommer, C. The Role of Mitogen-Activated Protein Kinase (MAPK) in Morphine Tolerance and Dependence. Mol Neurobiol 40, 101–107 (2009). https://doi.org/10.1007/s12035-009-8074-z

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