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Striatal dopamine D1 and D2 receptors are differentially regulated following buprenorphine or methadone treatment

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Abstract

Rationale

Chronic administration of morphine induces adaptations in neurotransmission system such as the dopamine pathway, and these modifications could be influenced by the drug administration pattern. Methadone and buprenorphine are the two main opioid substitution therapies, and despite their protracted use in humans, no study has investigated their ability to regulate dopamine system after chronic exposure/withdrawal.

Objectives

We evaluated the consequences of two administration patterns of methadone and buprenorphine on striatal dopamine D1 (D1R) and D2 (D2R) receptor levels.

Methods

Mice were treated with escalating doses of methadone or buprenorphine for 5 days either once daily (binge) or three times a day (TTD). D1R and D2R density in striatum was measured by autoradiography using [3H]-SCH23390 and [3H]-raclopride, respectively, at 1 (WD1), 14 (WD14), and 35 (WD35) days after the last opioid injection.

Results

A downregulation of D1R was observed upon TTD administration of buprenorphine and binge methadone treatment while an increase of those receptor levels was detected both with binge buprenorphine and TTD methadone treatments. Concerning the D2R, we rather measured an early or late downregulation with both agonists and administration patterns.

Conclusions

Our results demonstrated that methadone and buprenorphine were able to differentially regulate dopamine receptor density depending on the withdrawal period and the administration pattern.

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Acknowledgments

This work was supported by the foundation Bettencourt-Schueller (Prix Coup d’Elan).

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

    Stéphane Allouche, Thierry Le Marec, Florence Noble & Nicolas Marie

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

    Stéphane Allouche, Thierry Le Marec, Florence Noble & Nicolas Marie

  3. Université Paris Descartes, Laboratoire de Neuropsychopharmacologie des Addictions, Institut Médicament-Toxicologie-Chimie Environnement, Paris, France

    Stéphane Allouche, Thierry Le Marec, Florence Noble & Nicolas Marie

  4. Service de pharmacologie, CHU de Caen, France

    Antoine Coquerel

  5. UMR « COMETE », Université de Caen Basse-Normandie, Institut national de la santé et de la recherche médicale U 1075, 14032, Caen, France

    Antoine Coquerel

  6. 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. Stéphane Allouche
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  2. Thierry Le Marec
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  3. Antoine Coquerel
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  4. Florence Noble
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  5. Nicolas Marie
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Corresponding author

Correspondence to Florence Noble.

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Allouche, S., Le Marec, T., Coquerel, A. et al. Striatal dopamine D1 and D2 receptors are differentially regulated following buprenorphine or methadone treatment. Psychopharmacology 232, 1527–1533 (2015). https://doi.org/10.1007/s00213-014-3785-x

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  • DOI: https://doi.org/10.1007/s00213-014-3785-x

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