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Vol. 58, Issue 1, 159-166, July 2000
-Opioid Receptors: Relationships with µ-Related
Morphine Dependence
Département de Pharmacochimie Moléculaire et
Structurale, Institut National de la Santé et de la Recherche
Médicale U266, Centre National de la Recherche Scientifique
UMR8600, Université René Descartes, Unité de
Formation et de Recherche des Sciences Pharmaceutiques et
Biologiques, Paris, France (F.N., B.P.R.); Institute of Biochemistry,
Biological Research Center, Hungarian Academy of Sciences, Szeged,
Hungary (M.S.); and Laboratoire des Récepteurs et Protéines
Membranaires, Centre National de la Recherche Scientifique UPR 9050, Université Strasbourg 1, ESBS Pole API, Illkirch, France (B.K.)
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 
-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 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.
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