The field has made tremendous advances toward understanding the selective role of the D1+ and D2+ MSN subtypes in NAc and dStr in mediating the effects of drugs of abuse. In particular, recently developed tools that enable the selective manipulation of these cell-types have played a predominant role in obtaining the majority of this information. What are the next steps? Since the underlying molecular adaptations in drug addiction models are not static, but very dynamic, it is crucial to develop the capability to selectively manipulate signaling molecules of interest in D1+ vs. D2+ MSNs in a temporally precise way. DREADDs and optogenetic tools can help with this time scale manipulation. DREADD ligands can be administered at different time courses throughout drug behavioral paradigms to parcel out the selective role of signaling receptors in the two MSNs in drug models. Optogenetic tools in particular provide an extremely powerful means to temporally regulate not only neuronal activity but G-protein-coupled receptor signaling using OptoXRs (Airan et al., 2009), glutamatergic signaling(Volgraf et al., 2006; Numano et al., 2009), GABAergic signaling, and even certain intracellular
