To investigate the functional relevance of miR-212-induced amplification of CREB activity in vivo on the suppressive effects of this miRNA on cocaine intake, we examined the effects of overexpressing the CREB co-activator CRTC1 (TORC1) on cocaine intake in rats with restricted or extended cocaine access. It is known that CRTC overexpression increases CREB activity and that miR-212 increases CRTC1 expression (Hollander et al., 2010). Consistent with an important role for striatal CREB signaling in attenuating the motivational properties of cocaine, we found that striatal TORC1 overexpression decreased cocaine intake in extended but not restricted access rats. These findings support the hypothesis that miR-212 controls cocaine intake at least in part by amplifying the CREB-TORC signaling axis in striatum. Moreover, these findings provide compelling support for a key role for miR-212 in regulating the development of compulsive drug taking in rats, and perhaps in influencing vulnerability to cocaine addiction in human drug users.
