Recent findings support the conclusion of a more predominate role for D1+ MSNs in producing the reinforcing and sensitizing effect of drugs of abuse, with most robust molecular changes occurring in these MSNs. For instance, acute exposure to psychostimulants potently induces numerous signaling molecules including FosB, ERK, c-Fos, and Zif268 in the D1+ MSNs, while repeated cocaine preferentially induces ΔFosB and alters GABA receptor and other ion channel subunits in this cell-type as well (Robertson et al., 1991; Young et al., 1991; Berretta et al., 1992; Cenci et al., 1992; Moratalla et al., 1992; Hope et al., 1994; Bertran-Gonzalez et al., 2008; Heiman et al., 2008). Furthermore, disrupting or over-expressing specific molecules, such as ΔFosB, DARPP-32, or Nr3c1 (the glucocorticoid receptor), in D1+ MSNs typically mimics the drug-related behaviors observed when these alterations are made in a non-cell-type-specific manner, while disrupting such genes in D2+ MSNs often causes an opposite response (Fienberg et al., 1998; Kelz et al., 1999; Deroche-Gamonet et al., 2003; Zachariou et al., 2006; Ambroggi et al., 2009; Bateup et al., 2010). Nonetheless, we cannot rule out
