As was the case for modifications within the VTA, pharmacological and biochemical studies first suggested that alterations in excitatory, glutamatergic synaptic function within the NAc may be important for the behavioral adaptations elicited by administration of drugs of abuse (Vanderschuren and Kalivas, 2000; Wolf, 1998). Direct support for this hypothesis came from electrophysiological studies that used the same strategy as the ex vivo experiments performed in the VTA. Non-contingent administration of cocaine for 5 days caused a decrease in the AMPAR/NMDAR ratio at synapses on NAc MSNs when measured 24h later or after a single challenge dose of cocaine following a 10–14 day withdrawal period (Kourrich 2007; Thomas et al., 2001). This decrease was accompanied by a reduction in the magnitude of NMDAR-dependent LTD. Prolonged cocaine self-administration also reduced excitatory synaptic responses recorded extracellularly in the NAc shell (Schramm-Sapyta et al., 2006) and was associated with an inability to elicit LTD in both the core and the shell (Martin et al., 2006). LTD in the NAc core could still not be elicited even following 21 days of abstinence yet was
