To determine neuronal networks related to both impulsivity and heroin abuse, we compared differentially expressed genes derived from two ventral striatal microarrays— human heroin abusers versus matched controls and SHRs versus WKYs. While only 6.8% of the differentially expressed genes overlapped (Fig. 5a, Supplementary Table 2), not surprising given the clear differences in phenotype, the 442 shared genes were disproportionately targets of CREM and regulators of neuroplasticity related to actin cytoskeleton and focal adhesion (Fig. 5b, Supplementary Table 2). Intriguingly, this analysis highlighted adhesion-like G-protein-coupled receptor-3 (Adgrl3), an adhesion G-protein coupled receptor highly expressed in the striatum and implicated with ADHD31. Similar to Crem, SHRs exhibited significantly reduced AcbC Adgrl3 at baseline (t18=3.63, p=0.002, Fig. 5c), but were more sensitive to heroin’s acute effect (F1,19=5.31, p=0.033, Fig. 5c).
