Of course, synaptic adaptations are not the only mechanisms by which drugs of abuse can modify mesocorticolimbic DA system circuitry to cause long-lasting behavioral changes. In vivo exposure to addictive substances activate complex intracellular signaling cascades including transcription factors, cause changes in intrinsic membrane excitability, affect dendrite and spine structure, and influence the levels of extracellular glutamate via impairments in cysteine-glutamate exchange. These additional drug-induced adaptations have been the subject of several recent reviews, which attempt to integrate all of these findings into a coherent view of the neural circuit adaptations that mediate addiction (Russo et al., 2010; Kalivas et al., 2009; Wolf, 2010).
