OBJECTIVE To study the role of I1-Imidazoline receptor(I1R) in opioid dependence.METHODS Subcellular location of μ opioid receptor (MOR) and IRAS was investigated by immunocytochemistry.The interaction between MOR and IRAS was studied by co-immunoprecipitation and fluorescence resonance energy transfer (FRET).Further more, whether the interactions between IRAS and MOR would affect the signaling and the adaptation of MOR was studied in the cells expressing MOR and IRAS.RESULTS We found that MOR and IRAS colocalized in the HEK293 cells transfected MOR and IRAS and in the neurons of the cerebral cortex and hippocampus.Coimmu noprecipitation and FRET assays showed that there were interac tions between the IRAS and MOR.High concentration reductant DTT did not interrupt the interactions, suggesting that the inter actions were not mediated by disulfide hond.Further more, we found that the interactions did not influence the expression and affinity of MOR, as well as the activation of G proteins, adeny late cyclase and extracellular signal-regulated kinase (ERK)phosphorylation coupled to MOR after stimulated by DAMGO.However, over-expression of IRAS could attenuate DAMGO-in duced MOR desensitization and internalization, accelerate MOR resensitization in the cells co-expressing IRAS and MOR, which probably by increasing the rate of dephosphorylation and recy cling of MOR.The molecular mechanisms for that were on stud ying.CONCLUSION These findings indicate I1 R is an impor tant molecular to modulate opioid functions, and provide the further evidence to support Il R as a new target for treating opioid addiction.