A recent study shows that cocaine-induced potentiation of glutamatergic transmission in the NAcb requires persistent VTA potentiation (Mameli et al., 2009). Reversal of cocaine-induced potentiation in the VTA through activation of mGlu1 prevents enhanced glutamate function in the NAcb and attenuates reinstatement of cocaine-seeking behaviors. While the mechanism linking the VTA and NAcb is unclear, this study establishes a clear serial effect of cocaine on glutamate function in the VTA and NAcb. Thus, voluntary cocaine self-administration induces a long-lasting potentiation of glutamate function in the VTA and the NAcb and this persistent synaptic potentiation may be critical in the continued expression of drug craving. Moreover, inasmuch as dopamine signaling originating within the VTA plays an important role in signaling saliency about the environment (Schultz, 1998), the long-lasting potentiation onto VTA DA neurons following cocaine self-administration could act to selectively accentuate drug-related cues while de-emphasizing all other non-drug stimuli or cues. This is hypothesized to bias the animal s behavior toward drug-related stimuli while precluding expression of other behaviors. In essence, behavior flexibility is lost as the animal becomes increasingly focused
