LAUSR

ABSTRACT Changes in microRNA (miRNA)‐mediated gene expression in the nucleus accumbens (NAc) may play important roles in regulating drug addiction. MiR‐29c is a highly expressed miRNA in the human and rodent nervous systems where it plays a broad regulatory role. As the first step towards investigating potential functions of miR‐29c in methamphetamine (METH) addiction, we used C57BL/6 mice in a model of METH‐induced locomotor sensitization. We measured miR‐29c expression changes in the NAc of the mice after repeated‐intermittent METH exposure and acute METH administration respectively by using quantitative real‐time PCR (qPCR). We found that miR‐29c expression was significantly down‐regulated in the NAc of METH‐sensitized mice but not in the acute METH‐treated mice. Then, we tested the respective effects of miR‐29c over‐expression and inhibition in the NAc on METH‐induced locomotor sensitization. To reach this goal, we constructed adeno‐associated virus (AAV)‐expressing miR‐29c (AAV‐miR‐29c) and its corresponding inhibitor ‐ tough decoy (AAV‐anti‐miR‐29c TuD) to over‐express and inhibit miR‐29c, respectively. We found that AAV‐miR‐29c over‐expression in the NAc enhanced METH‐induced locomotor sensitization, whereas AAV inhibition of miR‐29c expression in the NAc attenuated the effects of METH. Moreover, we observed the participation of Dnmt3a, Dnmt3b, and Meg3 in the effects of miR‐29c on METH sensitization. Our results suggest that miR‐29c is an important epigenetic regulator of METH‐induced behavioural sensitization and changes in gene expression. These data further suggest a potential role of miR‐29c in regulating long‐term METH‐induced adaptation in the brain. HighlightsMETH induced significantly decreased expression of miR‐29c in the NAc.Over‐expression of miR‐29c in the NAc enhanced METH‐induced locomotor sensitization.Inhibition of miR‐29c in the NAc attenuated METH‐induced locomotor sensitization.Dnmt3a/b and Meg3 involved in miR‐29c‐regulating METH sensitization.