of these MOR-DOR heteromers has recently been implicated (He SQ et al. 2011) as playing a major role in opioid tolerance. DOR antagonists have been shown to block the sensitization to the conditioned rewarding effects of morphine that occurs with opioid pretreatment (Shippenberg, Chefer, & Thompson 2009). A recent report (Billa, Xia, & Morón 2010) found that administration of a DOR2 antagonist blocked morphine-induced CPP in rats and resulted in an increase in expression of the DOR dimer in the hippocampal postsynaptic density. These reports support a role for DORs in pathophysiology of opioid dependence which may be at least partially mediated by altered expression. In fact, a recent report proposing the design of an opioid drug that causes reduced tolerance and dependence advocated for drug development focused on DOR/MOR heteromers (Berger & Whistler 2010). Although MORs and DORs are generally considered to have synergistic antinociceptive effects (Zhang & Pan 2010), opposing effects on other behaviors such as impulsivity have been reported in rodents (Olmstead, Ouagazzal, & Kieffer 2009).
