To investigate the neurobiological implications of genetic associations and interactions, mRNA levels of DRD1, DLG4 and HOMER1 were examined throughout the striatum by ISHH in a subset of specimens from the Caucasian European Heroin postmortem collection (34 heroin and 19 control subjects). Of the glutamatergic markers, heroin subjects had decreased mRNA expression of DLG4 (P=0.028) and HOMER1 (P=0.006) in the putamen (Table 3), when compared to controls. A similar decrease of the HOMER1 mRNA levels was also detected in the caudate nucleus (P=0.030) as well as the NAc core (P=0.001) and shell (P=0.019). DRD1 mRNA was significantly decreased in the putamen of heroin abusers (P=0.008; Table 3). A similar decrease of DRD1 mRNA was also observed in the NAc shell (P=0.033) of heroin subjects. Urine morphine concentrations were correlated with HOMER1 mRNA expression levels in the caudate nucleus (r=0.459, P=0.018) and putamen (r=0.476, P=0.018); similar trend in the NAc. In addition, urine morphine concentration was positively correlated with DLG4 expression in the NAc shell (r=0.6959, P=0.001) and core (r=0.5376 P=0.017).