In summary, the pharmacological effect of cocaine and other drugs of abuse induce a transient potentiation of glutamatergic projections onto VTA DA neurons. Importantly, synaptic neuroadaptations induced through voluntary cocaine self-administration sessions are persistent, and remain potentiated despite extinction of cocaine-seeking behavior. Several important questions remain unanswered. Numerous brain regions are activated by drugs of abuse (Pierce and Kumaresan, 2006), many of which provide extensive excitatory projections onto VTA DA neurons (Colussi-Mas et al., 2007; Fields et al., 2007; Geisler et al., 2008). Traditional ex vivo electrophysiology techniques lack the precision to isolate region-specific afferents synapsing onto VTA DA neurons. Fortunately, with the development of optogenic approaches (Zhang et al., 2007), it is now possible to identify region-specific glutamatergic projections that may be differentially modulated by cocaine and other drugs of abuse. In addition, in vivo electrophysiological techniques (Lee et al., 2009) offer another promising tool in which drug-induced alterations in synaptic function can be examined in the intact animal. This technique will be especially useful to study drug-mediated changes in synaptic function between interconnected brain regions, which is not
