As noted above, an emerging theme in miRNA biology is the fact that miRNAs will often feed back onto the same signaling cascades that regulate their expression. The repressive effect of miRNAs on translation make them ideally suited to fulfill such feedback roles in moderating signaling cascades,118 which may serve to stabilize signaling cascades by protecting against random fluctuations and facilitate stable cellular states.133 Considering the pronounced effects of miR-212, and other miRNAs described above, in regulating the motivation to self-administer addictive drugs, our laboratory has investigated the transcriptional mechanisms by which miR-212 (and other miRNAs) expression is controlled. Loss-of-function mutations or duplications of the methyl CpG binding protein 2 (MeCP2) gene cause Rett syndrome (RTT) in humans,134,135 a neurodevelopmental disorder associated with severe mental retardation. MeCP2 is an epigenetic factor that binds to methylated cytosine residues of CpG dinucleotides 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
