Large and rapid dopamine increases in the mesocorticolimbic (MCL) system are thought to underlie the initial reinforcing effects of abused drugs (Nestler 2005). As such, preclinical and clinical studies have generally focused on neuroadaptations in midbrain dopaminergic areas (e.g., ventral tegmental area, substantia nigra pars compacta) and the structures to which they project (e.g., the nucleus accumbens [NAc] of the ventral striatum), following an extended history of drug administration (Everitt and Robbins 2005, Koob and Volkow 2010). While understanding of the molecular and cellular drug-induced changes within constituent components of the MCL system has advanced (Morón and Green, 2010), much less is known about the circuit-level manifestations of such regional alterations when considering interactions among and between MCL regions and other subcortical and cortical structures. Insofar as drug addiction has historically been viewed as a dopaminergic dysregulation disorder (Di Chiara et al., 2004; Wise, 2008), rsFC investigations have begun to interrogate the MCL system in the service of elucidating circuit-level alterations associated with reward deficits in the human addict.
