The most compelling evidence for the more robust role of D1+ MSNs in drug abuse comes from literature evaluating induction of intracellular signaling molecules. As stated above, acute doses of psychostimulants induce IEG expression, including c-Fos, Zif268 (Egr1), and FosB primarily in D1+ MSNs in NAc and dStr (Robertson et al., 1991; Young et al., 1991; Berretta et al., 1992; Cenci et al., 1992; Moratalla et al., 1992; Bertran-Gonzalez et al., 2008). This induction requires activation of D1 receptors, and the cell-type-specificity of the IEG induction in response to acute cocaine was recently confirmed using D1-GFP and D2-GFP reporter mice (Bertran-Gonzalez et al., 2008). Interestingly, the confirmation of cocaine’s induction of c-Fos primarily in D1-GFP throughout striatum with a small induction in D2-GFP MSNs only in dStr was confirmed using a context-dependent paradigm (mice were injected in a novel environment outside of their home cage). Furthermore, a previous study using in situ hybridization in mice also showed induction of c-Fos in D1+ and D2+ MSNs in dStr, although in this study representative bar graphs show greater number of D1+ c-Fos
