The Role And Mechanism Of Metformin In Methamphetamine Dependence

Objective:Explore the potential role and mechanism of metformin in methamphetamine(MA)dependence.Methods:Established methamphetamine-induced CPP model and verified the effect of metformin in CPP score.Established MA withdrawal model,observed the changes in immobility time in Tail suspension test(TST)and Forced swimming test(FST),and changes of duration mice stayed and the times mice entered to the open arms in elevated plus maze(EPM).Western blotting(WB)technique was used to detect the expression and activity of AMP-activated protein kinase(AMPK),the related inflammatory factor interleukin 1β(Interleukin-1β,IL-1β)and cyclooxygenase-2(COX-2)expression in the hippocampus of mouse brain to explore the effects of metformin in chronic MA exposure.Results:Metformin treatment promoted the distinction,and inhibited the priming while not affecting the formation in MA induced CPP model.In the MA withdrawal model,metformin reduced the depression and anxiety-like behaviors caused by MA withdrawal,manifested by a reduction in immobility time in FST and TST,as well as an increase in the duration mice stayed and the times mice entered to the open arms in EPM experiment.In WB experiment,we found that metformin enhanced MA-induced increased AMPK phosphorylation(Thr-172)and reduced the expression of inflammatory factors like IL-1βand COX-2 in mouse hippocampus.Conclusions:metformin can inhibit the priming period and promote the distinction in MA induced CPP model;metformin can alleviate the depressive-like and anxiety-like behaviors induced by MA withdrawal and inhibited the expression of inflammatory factors.Therefore,metformin may participate in the occurrence and development of MA dependence by regulating the expression of inflammatory factors in the hippocampus.