Brain imaging studies have shown that cue-elicited craving is associated not only with increased activation of the NAc (34–36), but also with activation of other reward regions including the VTA, orbitofrontal cortex, insula, and ACC (37–40). This suggests that processing of conditioned responses in the brain (as well as processing of reward) is the result of functional networks that include cortical and subcortical brain regions rather than involvement of isolated brain regional effects. Indeed, preclinical studies have revealed that glutamatergic projections from the prefrontal cortex (PFC) into the VTA/SN, NAc, and dorsal striatum as well as projections from the amygdala to the NAc are involved in these conditioned responses (10).
