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 across a wide-range of cocaine doses (Schaefer et al., 2010). Such downward shifts in the cocaine dose-response curve are interpreted as reduced motivation to consume the drug. Finally, Ago2 ablation in D2R MSNs dramatically decreased miRNA expression and activity in striatum. Hence, as cocaine self-administration behavior is considered the most direct measure of drug reinforcement in laboratory animals, these data provide compelling support for a key role for Ago2, and by extension miRNAs, in striatal MSNs in regulating the reinforcing properties of cocaine that drive the development of addiction (Schaefer et al., 2010).
