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.