Overexpression of dynamin is induced by chronic stimulation of mu- but notdelta-opioid receptors: Relationships with mu-related morphine dependence

Several studies using selective opioid agonists or mice with a deletion of the mu-opioid receptor, have shown that morphine dependence is essentially due to chronic stimulation of mu- but not delta-opioid receptors. Because d ependence is assumed to be related to persistent intracellular modification s, we have investigated modifications putatively induced by chronic activat ion of mu receptors with morphine or selective agonists in vitro in SH-SY5Y cells and in vivo in different strains of mice, including mice lacking the mu-opioid receptor gene. The results show a similar down-regulation and de sensitization of mu and delta binding sites, whereas an overexpression of d ynamin occurred only with mu agonists, strongly suggesting the relevance of this upregulation with the opiate dependence. Moreover, translocation of o verexpressed dynamin from intracellular pools to plasma membranes was obser ved in chronic morphine-treated rats. This recruitment could be critically involved in long-lasting changes such as alterations of axonal transport ob served in opioid dependence.