The Effects Of GSK-3? In Chronic Methamphetamine-induced Rats' Protracted Syndrome After Withdrawal

Objective As a chronic,recurring encephalopathy,drug addiction is a global public health issue.Relapse is an important charactor of drug dependence.Drug addiction treatment is the key to the prevention and treatment of relapse after detoxification.Therefore,This project works up methamphetamine withdrawal model in rats.It focuses on that relationship between the delayed effects of chronic methamphetamine in the hippocampus and the treatment of the GSK-3? and its phosphorylated form and circadian gene,Bmal1.It provide a new way to develop effective anti-relapse therapy.Methods 1.Male Sprague-Dawley rats(200-250g)were fed in a 12h/12 h light/dark circulat ion 7 days.It was divided into the methamphetamine withdrawal group and sal ine group randomly,then,we made a open field and conditioned place preferen ce(CPP)tests.The addictive rats were prepared by conditioned place preferenc-e box and a 2-week alternating intraperitoneal injection with methamphetamine(3mg/kg)or saline(1ml/kg),another one were injected with saline.then,we ma de a post-test about open field and CPP tests.After a 10-days' withdrawal,tak-e out the hip in ZT4 of the two group rats,and detect the protein expression of hippocampus Bmal1 by Western Blot.2.The SD rats were randomly divided into methamphetamine withdrawal menstruum group ? methamphetamine inhibitor group and saline menstruum group ? saline inhibitor group after feeding the 12h/12 h light/dark circulation of 7d.After we built the methamphetamine addiction model,Brian stereotaxic surgeries to GSK-3? inhibitor SB216765 were performed for micro-injection in Hip.After a 10-days` withdrawal,we tested CPP score,and detect the protein expression of hippocampus Bmal1 by Western Blot.Results 1.Meth significantly enhanced the effect of conditioned place preference in rats(p<0.05),which indicated that the methamphetamine addiction model was established.2.Open field test indicated that the reduction of explotatory behavior in methwithdrawal rats(p<0.05).3.the level of GSK-3? ? p-GSK3? and Bmal1 did significantly reduction in methwithdrawal rats compared with control rats(p<0.05).4.After stereotaxic surgeries,there was no significant change in the expression of Bmal1 in saline menstruum group and saline inhibitor group;but in another one,the Bmal1 was higher in methamphetamine withdrawal inhibitor group than in methamphetamine withdrawal menstruum group(Hip)(p<0.05).Conclusion GSK-3??p-GSK3? and Bmal1 had significantly effects on the phosphorylated form in methamphetamine addiction,Micro-injection of GSK-3? inhibitor SB216765,which made the expression of the circadian gene change.