Background:　Repeated　exposure　to　addictive　drugs　elicits　long-lasting　cellular　and　molecular　changes.　It　has　been　reported　that　the　aberrant　expression　of　long　non-coding　RNAs　(lncRNAs)　is　involved　in　cocaine　and　heroin　addiction,　yet　the　expression　profile　of　lncRNAs　and　their　potential　effects　on　methamphetamine　(METH)-induced　locomotor　sensitization　are　largely　unknown.　Results:　Using　high-throughput　strand-specific　complementary　DNA　sequencing　technology　(ssRNA-seq),　here　we　examined　the　alterations　in　the　lncRNAs　expression　profile　in　the　nucleus　accumbens　(NAc)　of　METH-sensitized　mice.　We　found　that　the　expression　levels　of　6246　known　lncRNAs　(6215　down-regulated,　31　up-regulated)　and　8442　novel　lncRNA　candidates　(8408　down-regulated,　34　up-regulated)　were　significantly　altered　in　the　METH-sensitized　mice.　Based　on　characterizations　of　the　genomic　contexts　of　the　lncRNAs,　we　further　showed　that　there　were　5139　differentially　expressed　lncRNAs　acted　via　cis　mechanisms,　including　sense　intronic　(4295　down-regulated　and　one　up-regulated),　overlapping　(25　down-regulated　and　one　up-regulated),　natural　antisense　transcripts　(NATs,　148　down-regulated　and　eight　up-regulated),　long　intergenic　non-coding　RNAs　(lincRNAs,　582　down-regulated　and　five　up-regulated),　and　bidirectional　(72　down-regulated　and　two　up-regulated).　Moreover,　using　the　program　RNAplex,　we　identified　3994　differentially　expressed　lncRNAs　acted　via　trans　mechanisms.　Gene　ontology　(GO)　and　KEGG　pathway　enrichment　analyses　revealed　that　the　predicted　cis-　and　trans-associated　genes　were　significantly　enriched　during　neuronal　development,　neuronal　plasticity,　learning　and　memory,　and　reward　and　addiction.　Conclusions:　Taken　together,　our　results　suggest　that　METH　can　elicit　global　changes　in　lncRNA　expressions　in　the　NAc　of　sensitized　mice　that　might　be　involved　in　METH-induced　locomotor　sensitization　and　addiction.