The expression mechanisms of the drug-evoked plasticity at excitatory synapses on VTA DA neurons have also been explored. Because the original report of a cocaine-induced increase in the AMPAR/NMDAR ratio suggested that this was due to an upregulation of AMPARs, it was surprising to find that in mice treated with cocaine the AMPAR EPSCs exhibited a partial inward rectification (Bellone and Lüscher, 2006) which is a hallmark of GluA2-lacking AMPARs (Isaac et al., 2007; Liu and Zukin, 2007). The presence of such AMPARs was confirmed by the sensitivity of the EPSCs to external polyamine toxines such as Joro spider toxin as well as an increased single channel conductance estimated using non-stationary fluctuation analysis (Mameli et al., 2007). While immunohistochemical staining with light-microscopic resolution failed to reveal changes in AMPAR subunit expression (Lu et al., 2002), immunogold labeling at the electron microscopy level did show an increase of GluA1 after morphine treatment (Lane et al., 2008) and that cocaine treatment causes a decrease of GluA2 content at synapses (Mameli et al., 2007; Brown et al., 2010). These results are consistent with
