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Research ArticleArticle

Overexpression of Dynamin Is Induced by Chronic Stimulation of μ- but Not δ-Opioid Receptors: Relationships with μ-Related Morphine Dependence

Florence Noble, Maria Szücs, Brigitte Kieffer and Bernard P. Roques
Molecular Pharmacology July 2000, 58 (1) 159-166; DOI: https://doi.org/10.1124/mol.58.1.159
Florence Noble
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Maria Szücs
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Brigitte Kieffer
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Bernard P. Roques
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Abstract

Several studies using selective opioid agonists or mice with a deletion of the μ-opioid receptor, have shown that morphine dependence is essentially due to chronic stimulation of μ- but not δ-opioid receptors. Because dependence is assumed to be related to persistent intracellular modifications, we have investigated modifications putatively induced by chronic activation of μ receptors with morphine or selective agonists in vitro in SH-SY5Y cells and in vivo in different strains of mice, including mice lacking the μ-opioid receptor gene. The results show a similar down-regulation and desensitization of μ and δ binding sites, whereas an overexpression of dynamin occurred only with μ agonists, strongly suggesting the relevance of this up-regulation with the opiate dependence. Moreover, translocation of overexpressed dynamin from intracellular pools to plasma membranes was observed in chronic morphine-treated rats. This recruitment could be critically involved in long-lasting changes such as alterations of axonal transport observed in opioid dependence.

Footnotes

    • Received December 3, 1999.
    • Accepted March 13, 2000.
  • Professor B. P. Roques, Institut National de la Santé et de la Recherche Médicale U266, Centre National de la Recherche Scientifique UMR 8600, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France. E-mail:roques{at}pharmacie.univ-paris5.fr

  • This work was supported by institutional grants from Centre National de la Recherche Scientifique and INSERM (France), grants from the European Community (BMH4 CT98 2267), and research grants OTKA T-16084, TÉT JFNo. 564. A short travel fund was provided by the French Embassy (Service Culturel, Scientifique et de Coopération) to M. Szücs.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 58 (1)
Molecular Pharmacology
Vol. 58, Issue 1
1 Jul 2000
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Research ArticleArticle

Overexpression of Dynamin Is Induced by Chronic Stimulation of μ- but Not δ-Opioid Receptors: Relationships with μ-Related Morphine Dependence

Florence Noble, Maria Szücs, Brigitte Kieffer and Bernard P. Roques
Molecular Pharmacology July 1, 2000, 58 (1) 159-166; DOI: https://doi.org/10.1124/mol.58.1.159

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Research ArticleArticle

Overexpression of Dynamin Is Induced by Chronic Stimulation of μ- but Not δ-Opioid Receptors: Relationships with μ-Related Morphine Dependence

Florence Noble, Maria Szücs, Brigitte Kieffer and Bernard P. Roques
Molecular Pharmacology July 1, 2000, 58 (1) 159-166; DOI: https://doi.org/10.1124/mol.58.1.159
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