Only a handful of studies report drug-evoked synaptic plasticity in neurons of the PFC. Applying biochemical methods to PFC tissue, and isolating a synaptic membrane preparation, it was proposed that GluA2 was endocytosed when cues previously associated with heroin self-administration were presented to a rat (Van den Oever et al., 2008). These findings were paralleled by a decrease in the AMPAR/NMDAR ratio measured in acute PFC slices, while self-administration of heroin alone did not affect synaptic strength. Other studies focusing on withdrawal from cocaine performed immunoblotting assays for several synaptic proteins in the dorsal medial PFC and reported an increased expression of NR2B at 14 days, and NR2A at 60 days of withdrawal (Ben-Shahar et al., 2009). Subcellular fractionation techniques revealed a significant increase in the trafficking of these receptors into the synaptosomal compartment (Ghasemzadeh et al., 2009).
