Ago2 and Dicer1 are involved in METH‐induced locomotor sensitization in mice via biogenesis of miRNA

Abstract microRNA (miRNA) play important roles in drug addiction and act as a post‐transcriptional regulator of gene expression. We previously reported extensive downregulation of miRNAs in the nucleus accumbens (NAc) of methamphetamine (METH)‐sensitized mice. However, the regulatory mechanism of this METH‐induced downregulation of miRNAs has yet to be elucidated. Thus, we examined METH‐induced changes in the expression of miRNAs and their precursors, as well as the expression levels of mRNA and the proteins involved in miRNA biogenesis such as Dicer1 and Ago2, in the nucleus accumbens of METH‐induced locomotor sensitized mice. miRNAs and Ago2 were significantly downregulated, while the expression of miRNA precursors remained unchanged or upregulated, which suggests that the downregulation of miRNAs was likely due to a reduction in Ago2‐mediated splicing but unlikely to be regulated at the transcription level. Interestingly, the expression level of Dicer1, which is a potential target of METH‐induced decreased miRNAs, such as miR‐124, miR‐212 and miR‐29b, was significantly increased. In conclusion, this study indicates that miRNA biogenesis (such as Ago2 and Dicer1) and their miRNA products may have a role in the development of METH addiction.