Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats

CONTEXT: MicroRNA (miRNA) is an important regulator of gene expression. Methamphetamine (METH) induces a variety of alterations in different systems by affecting gene expression, but the effects of METH on miRNA profiles need to be elucidated. OBJECTIVES: This study develops a rat model of METH addiction, and analyzes the expression profile alterations of miRNA in nucleus accumbens (NAc) of the METH-addicted rats. MATERIALS AND METHODS: Sprague-Dawley rats were administered 10 mg/kg METH or vehicle twice a day for 4 weeks. The addictive behaviour of rats was estimated by CPP test. The pathological changes of brain tissues were then observed by HE and Glee silver staining. The miRNA profile analysis of the NAc of the rats was performed using an Illumina HiSeq™ 2500 sequencing system. RESULTS: CPP test indicated that METH significantly prolonged the residence time of the rats in the drug box (from 307 ± 97 to 592 ± 96 s). The pathological staining showed the distorted axons, and fewer polarized neurons in the METH-treated rats. We further identified 40 differential miRNAs (17 up- and 23 down-regulated) and three novel miRNAs (novel 237, 296 and 501) that responded to METH. The bioinformatic analysis for the potential targets of the differential miRNA suggests that the downstream were concentrated in the Wnt signalling pathway, tuberculosis, toxoplasmosis, spliceosome, lysosome, and axon guidance. DISCUSSION AND CONCLUSIONS: A number of miRNAs responding to METH were identified in the NAc of rats. These METH-regulated miRNAs provide a new perspective for revealing the molecular mechanisms of METH addiction.