in DNA and can recruit HDACs and other transcriptional repressors to inactivate target gene expression.136 Interestingly, MeCP2 expression is known to be negatively regulated by miR-212.137 We found that MeCP2 level's were increased in the striatum of rats with extended but not restricted daily access to cocaine,137 and that virusmediated knockdown of MeCP2 in striatum enhanced the effects of cocaine on miR-212 expression.138 We also found that MecP2 knockdown in striatum dramatically decreased cocaine intake in rats. This effect was reversed by antisense oligonucleotide-mediated inhibition of miR-212 signaling expression.137 These findings suggest that MecP2 attenuates cocaine-induced increases in miR-212 activity and increases the motivation to consume cocaine and that, in turn, miR-212 negatively regulates MeCP2 expression. Hence, homeostatic interactions between miR-212 and MeCP2 are likely to play an important role in regulating sensitivity to the motivational effects of cocaine.
