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Chronic and intermittent morphine treatment differently regulates opioid and dopamine systems: a role in locomotor sensitization

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Abstract

Rationale

Behavioral sensitization induced by repeated morphine administrations may depend on patterns of administration. However, neurobiological mechanisms involved in this sensitization are largely unknown.

Objectives

We compared the effects of intermittent (20 mg/kg, once daily for 7 days) and chronic (escalating doses from 5 to 40 mg/kg, three times a day for 5 days) morphine treatments in mice on locomotor activity. We also quantified, by autoradiography, mu opioid receptor (MOR) in ventral tegmental area (VTA), dopamine D1 (D1R) and D2 (D2R) receptors in striatum.

Results

Whereas the intermittent treatment led to a long-term sensitization to locomotor effects of morphine [until withdrawal day (WD) 14], the chronic treatment induced a tolerance (WD1) followed by a transient sensitization (WD14). Binding studies demonstrated a decrease of MOR in VTA at WD1 for the chronic treatment. In contrast, striatal D1R level was decreased at WD1, and increased at WD14 for the chronic treatment. For the D2R, we observed a decrease from WD1 to WD14 for the intermittent treatment and an increase at WD1 followed by a decrease at WD14 for the chronic treatment.

Conclusions

These results demonstrate that chronic and intermittent morphine treatments could induce different behavioral adaptations that could be explained in part by distinct changes occurring in dopamine and opioid systems.

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Acknowledgments

Thierry Le Marec was a recipient of a fellowship from the Fondation pour la Recherche Médicale. The authors wish to thank Dr. Ana Cardona (Unité de Recherche et d'Expertise Histotechnologie et Pathologie, Institut Pasteur, Paris) for her help on Beta imager and helpful comments on the manuscript. The authors would also like to thank the quantitative real-time PCR and animal care facilities of the Institut Médicament-Toxicologie-Chimie Environnement (IMTCE), Université Paris Descartes, Paris, France.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8206, Paris, France

    Thierry Le Marec, Cynthia Marie-Claire, Florence Noble & Nicolas Marie

  2. Institut national de la santé et de la recherche médicale U 705, Paris, France

    Thierry Le Marec, Cynthia Marie-Claire, Florence Noble & Nicolas Marie

  3. Université Paris Descartes, Laboratoire de Neuropsychopharmacologie des Addictions, Institut Médicament-Toxicologie-Chimie-Environnement, 4 avenue de l’Observatoire, 75006, Paris, France

    Thierry Le Marec, Cynthia Marie-Claire, Florence Noble & Nicolas Marie

  4. Laboratoire de neuropsychopharmacologie des addictions, CNRS UMR 8206-INSERM U 705, Faculté de Pharmacie, 4, avenue de l’Observatoire, 75006, Paris, France

    Florence Noble

Authors
  1. Thierry Le Marec
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  2. Cynthia Marie-Claire
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  3. Florence Noble
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  4. Nicolas Marie
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Correspondence to Florence Noble.

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Le Marec, T., Marie-Claire, C., Noble, F. et al. Chronic and intermittent morphine treatment differently regulates opioid and dopamine systems: a role in locomotor sensitization. Psychopharmacology 216, 297–303 (2011). https://doi.org/10.1007/s00213-011-2223-6

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  • DOI: https://doi.org/10.1007/s00213-011-2223-6

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