The PFC works in tandem with striatal regions via corticostriatal networks that are modulated by DA (42). Imaging studies have documented disruption of these complex pathways, which have been investigated predominantly for the D2R-mediated signaling pathways and to a limited extent for the D1R-signaling pathway. In addicted subjects (to various drug classes including cocaine, heroin, alcohol, methamphetamine, nicotine, cannabinoids), a consistent finding reported from PET studies and corroborated by preclinical studies of chronic drug administration is that of significant reductions in D2R availability in the striatum, which persists months after detoxification (reviewed in Reference 19). Brain imaging studies on the effects of chronic drugs on D1R are few, and results are not always consistent. Specifically, in studies with nonhuman primates that were chronically exposed to cocaine, some investigators reported increases in D1R (43, 44), whereas others reported decreases (45). The conflicting reports suggest that the availability of D1R could be very sensitive to the characteristics (e.g., dosage, duration, frequency, and abstinent periods) of cocaine administration (46). In humans, imaging (PET) studies of cocaine abusers reported no changes in D1R (46), and postmortem studies of cocaine abusers and alcoholics reported no changes in D1R protein or mRNA (47).
