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 a scenario whereby GluA2 containing receptors are exchanged for GluA2 lacking ones and no significant increase in the number of synaptic AMPARs occurs. The insertion of GluA2 lacking AMPARs which are highly conductive at negative potentials but carry minimal current at positive potentials can explain an increase of the AMPAR/NMDAR ratio when calculated at -70 mV / +40 mV but not when both components are measured at +40 mV. This raises the possibility that cocaine administration may also decrease the number and/or function of synaptic NMDARs, which is supported by the recent observation of a decrease in unitary NMDAR-EPSCs following cocaine treatment (Mameli et al., 2011). This study also examined the functional consequences for further activity-dependent synaptic plasticity. While in slices an induction protocol that depolarizes DA neurons led to LTP, thus obeying a Hebbien induction rule, this protocol was inefficient after cocaine treatment. Conversely a slight hyperpolarization of the DA neurons during afferent stimulation (i.e. “anti-Hebbian” coincidence) induced a
