Our immunohistochemistry experiments demonstrated that the mu-opioid receptor co-localized with the dopamine D₁ receptor in neurons of the cortex and caudate nucleus. On the basis of this physiological data we further investigated whether these two G protein coupled receptors formed hetero-oligomers in living cells. To demonstrate hetero-oligomerization we used a novel strategy, the method used harnessed the physiological cellular mechanism for transport of proteins to the nucleus. The nuclear translocation pathway was adapted for the visualization of mu-opioid hetero-oligomers with the dopamine D₁ receptor. The receptor hetero-oligomer complex formed resulted in a significantly enhanced surface expression of mu-opioid receptor. This hetero-oligomer formation involved the interaction of mu-opioid receptor with the dopamine D₁ receptor carboxyl tail, since a dopamine D₁ receptor substituted with the carboxyl of the dopamine D₅ receptor failed to increase surface expression of mu-opioid receptor.