MicroRNAs　(miRNAs)　are　modulators　of　gene　expression　that　play　key　regulatory　roles　in　distinct　cellular　processes.　Methamphetamine　(METH)　induces　various　aberrant　changes　in　the　limbic　system　by　affecting　a　complex　gene　regulatory　mechanism,　yet　the　involvement　of　miRNAs　in　the　effects　of　METH　exposure　remains　unclear.　This　study　identifies　METH-responsive　miRNAs　and　their　potential　effects　in　the　nucleus　accumbens　(NAc)　of　mice.　Using　miRNA　sequencing,　we　examined　the　expression　of　miRNAs　in　the　NAc　of　saline-　and　METH-treated　mice　and　identified　45　known　miRNAs　to　be　METH　responsive.　Additionally,　we　identified　two　novel　miRNA　candidates　that　were　METH　responsive　(novel-m002C　and　novel-m009C).　Our　target　prediction　analysis　suggested　that　the　known　METH-regulated　miRNAs　might　target　genes　that　are　involved　in　cellular　autophagy,　cellular　metabolism,　and　immune　responses　and　that　the　novel　METH-regulated　miRNA　candidates　might　target　genes　that　are　related　to　drug　addiction.　We　also　matched　the　predicted　targets　of　METH-regulated　miRNAs　with　the　NAc　messenger　RNA　expression　profile,　revealing　eight　putative　METH-regulated　target　genes　(Arc,　Capn9,　Gbp5,　Lefty1,　Patl2,　Pde4c,　Strc,　and　Vmn1r58).　Thus,　METH　triggers　an　alteration　in　NAc　miRNA　expression,　which　could　contribute　to　METH-induced　changes　in　neuron　autophagy,　metabolism,　and　immune　responses.　The　differential　expression　of　putative　target　genes　suggests　their　involvement　following　exposure　to　METH.　(c)　2015　Wiley　Periodicals,　Inc.