Drugs of abuse exert potent molecular and cellular alterations in both dorsal striatum (dStr) and ventral striatum (nucleus accumbens, NAc), and many of these changes occur in medium spiny neurons (MSNs), the principal projection neurons in dStr and NAc, which account for 90–95% of all neurons in these regions. However, researchers have until recently been unable to clearly define the differential role of the two MSN subtypes in addiction-related phenomena. The two MSN subtypes are differentiated by their enrichment of dopamine receptor 1 (D1) or dopamine receptor 2 (D2) as well as several other genes (Gerfen and Young, 1988; Gerfen et al., 1990; Le Moine et al., 1990, 1991; Bernard et al., 1992; Ince et al., 1997; Lobo et al., 2006, 2007; Heiman et al., 2008; gensat.org) and by their distinct projections through the cortico-basal ganglia pathway (the direct vs. indirect pathways; Gerfen, 1984, 1992). Early work suggested that drugs of abuse exert most influence on the D1+ MSNs, with the use of numerous dopamine receptor agonists and antagonists providing important insight into the functional and molecular roles of each
