In the 90’s, based primarily on pharmacological manipulations and biochemical assays as well as the excitement generated by the elucidation of some of the mechanisms and putative function of hippocampal LTP and LTD, it was proposed that modifications of excitatory synaptic transmission in the mesolimbic DA system are important for the neural circuit adaptations underlying some of the long-lasting behavioral consequences of administration of drugs of abuse, in particular psychostimulants (Overton et al., 1999; Wolf, 1998; Kalivas, 1995). A direct test of this hypothesis was subsequently performed and resulted in the first characterization of a form of drug-evoked synaptic plasticity (Ungless et al., 2001). The experimental approach, now standard, involved preparing acute midbrain slices from an animal that 24 hours earlier had received a single non-contingent injection of cocaine (or saline) and recording from VTA DA neurons. As a surrogate measure of synaptic strength, the authors measured the ratio of the AMPA receptor-mediated ESPC (AMPAR EPSC) to the NMDA receptor-mediated EPSC (NMDAR/EPSC); the so-called AMPAR/NMDAR ratio. This ratio was significantly increased for approximately a week following the injection of cocaine
