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
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|