The Effects Of MiR-219a-5p On Methamphetamine Addiction

Objective:Methamphetamine(METH)dependence is a serious public health problem,which also can result in many mental disorder,but the molecular mechanism in this process remains unclear.This article is aim to discover the effects of microRNA in METH addiction by target the rein-angosinten system(RAS).Methods:1.The aberrant expression of microRNAs were determined by comparing among METH self-administration(METH SA),METH-yoked and Saline-yoked.This experiment revealed the microRNAs related with RAS by the GO and KEGG analysis.2.MiR-219a-5p were overexpressed in nucleus accumbens(NAc)by lentivirus vector to determine the effects of miR-219a-5p in Fixed Ratio(FR),Progressive Ratio(PR)and reinstatement.3.MiR-219a-5p were overexpressed in nucleus accumbens(NAc)by lentivirus vector to determine the effects of miR-219a-5p in reinstatement.4.Angiotensin II receptor type 1(AT1),phosphatidylinositol phospholipase C beta(PLC?)and cAMP-response element binding protein(CREB)were examined by enzyme-linked immunosorbent assay(ELISA).5.The level of AT1,PLC? and CREB were tested by western blotting(WB).Results:The results suggest that multiple miRNAs were aberrantly expressed in rat NAc compared with METH-yoked and Saline-yoked.miR-219a-5p was found by p-vale and fold change which downregulated in NAc and regulated the expression of angiotensin II receptor type 1b(AT1bR).The overexpression of miR-219a-5p significantly decreased the number of responses in FR,PR in the 0.05,0.075 and 0.1mg/kg and the breakpoints in reinstatement.The expression of AT1,PLC?and CREB was increased significantly compared with saline group.The overexpression of miR-219a-5p significantly decreased the level of AT1,PLC? and CREB.Conclusion:Our findings suggest that NAc miR-219a-5p plays an important role in brain reninangiotensin-aldosterone system(RAAS),reveal novel molecular regulators that control the complex actions of METH addiction,and provide an entirely new direction for the development of anti-addiction therapeutics based on modulation of noncoding RNAs.