In a study by Schaefer et al. it was shown that cocaine-induced robust alterations in the expression of a wide-range of miRNAs in the striatum, a key brain site involved in addiction. Indeed, a subset of these miRNAs whose expression was impacted by cocaine were shown to regulate the expression levels of a wide-range of genes known to influence the motivational properties of cocaine, including Bdnf, FosB (FBJ murine osteosarcoma viral oncogene homolog B), and Cdk5r1 (cyclin-dependent kinase 5 activator 1). In the same study, the effects on cocaine reinforcement of selectively ablating Ago2, the catalytic component of RISC involved in transducing the inhibitory actions of miRNAs on their target transcripts, was assessed. Specifically, Schaefer et al. investigated the effects knocking down Ago2 in medium spiny neurons (MSNs) of the striatum that express the dopamine D2 receptor (D2R) (Schaefer et al., 2010). Disruption of Ago2 in D2R MSNs resulted in dramatically reduced conditioned rewarding effects of cocaine in mice, reflected in attenuated cocaine-induced conditioned place preference (CPP). More importantly, the Ago2-D2R mutant mice also demonstrated reduced intravenous cocaine self-administration behavior
