Two recent studies from our group have identified a key role for miR-212, also encoded by the miR-212/132 gene cluster, in regulating compulsive-like cocaine intake in rats (Hollander et al., 2010; Im et al., 2010). As described above, the striatum is a key brain region that regulates compulsive cocaine use. The first study showed that in rats with extended access to cocaine (6 h per day) there is a ∼1.75-fold increase in both striatal miR-212 and miR-132 levels (Hollander et al., 2010). Similar increases in expression were not detected in rats that received non-contingent cocaine infusions time-locked to rats that volitionally consumed cocaine, or in rats with restricted access to cocaine (1 h per day). Further, lentivirus-mediated overexpression of miR-212 in the dorsal striatum resulted in a remarkable decrease in cocaine intake in the extended access rats compared to vector control, but overexpression did not alter cocaine intake in rats with restricted drug access (Figure 2). The decreased cocaine intake is related to a profound decrease in the motivational properties of the drug, as reflected by a large downward shift
