miRNAs expression profile in heroin self-administration

MicroRNAs (miRNAs) are small (s21–23 nucleotides) ncRNAs single-stranded transcripts that regulate gene expression at the post-transcriptional level through target mRNA degradation or translational inhibition. It has been reported that differential miRNA expression is mediated by drugs/addictive substances. Heroin addiction is thought to induce long term neuroadaptative modifications in brain reward related areas but the role of miRNA in these modifications is unknown. To investigate this role, we have performed a genome-wide analysis on 736 mature miRNAs in rats self-administering heroin i.v. (SA). Analysis by RT-PCR revealed that heroin SA was associated to up- or down- regulation of different miRNAs in the prefrontal cortex, n. accumbens (shell and core) and dorsal caudate-putamen (CPu). We also identified target genes and their expression profiling was performed using specific RT primers. Moreover we analized the expression of respective proteins by Western Blot. We found 51 miRNAs disregulated in PFCx (39 up, 12 down), 125 in CPu (105 up, 20 down), 39 in NAc Shell (16 up, 23 down) and 114 in NAc Core (97 up, 17 down) correlated with a disregulation of the expression of several genes such as Drd3 (DAD3receptors), Bdnf, Cckbr, Mecp2 and Nos1. These results suggest that some miRNAs are key regulators of the reward circuits and that they could be involved in the long term neuroadaptative modifications induced by heroin exposure