Potentiation of AMPAR-mediated responses in VTA DA neurons is observed 24 hrs following single or multiple non-contingent cocaine injection (Argilli et al., 2008; Borgland et al., 2004; Ungless et al., 2001). Cocaine-induced AMPAR potentiation is mediated through enhanced trafficking of GluA2-lacking AMPA receptors into the synapse (Figure 2B; Argilli et al., 2008; Bellone and Lüscher, 2006). In addition, this increase in synaptic AMPARs is indicative of synapses in a potentiated state, which can prevent further synaptic plasticity (Argilli et al. 2008). Importantly, activation of mGlu1 reverses cocaine-induced potentiation through the exchange of GluA2-lacking AMPARs with GluA2-containing AMPARs (Bellone and Lüscher, 2006; Mameli et al., 2007), restoring these synapses back to their pre-drug states.
