Analysis of postmortem midbrain (Tang et al., 2003) and NAcb (Hemby et al., 2005) tissue collected from human cocaine-overdose victims has revealed significant upregulation of CREB and GluA2. While ΔFosB accumulation may reflect an important mechanism contributing to the transition from drug use to drug abuse (Nestler, 2001), the extent of postmortem ΔFosB accumulation in human cocaine addicts has not been determined. Additionally, given that the majority of studies observing increased AMPAR function after drug exposure have found a decrease rather than an increase in GluA2 function, the functional relevance of these CREB and Fos family-mediated GluA2 AMPA subunit changes remains to be fully elucidated. Finally, though intriguing parallels can be drawn between identified roles of CREB, ΔFosB, and AMPA receptor subunits in addiction-associated behaviors, it has not yet been determined if CREB, ΔFosB, and AMPARs lie within the same molecular network.
