PER1 Mediated Chronic Methamphetamine-induced Rats' Behavior Change After Withdrawal

Objective : Drug addiction is a chronic relapsing encephalopathy.Circadian gene regulation of biological rhythms could make the organisms more adapt to the environment,it also played an important role in the drug dependence.Drug dependence has highly disrupted rhythms and it was likely that chronic disruption or particular chronotypes may increase the vulnerability for addiction and relapse.However,the mechanisms of circadian genes regulate drug reward remain not clearly understood.We perfomed conditioned place preference assays to establish the methamphetamine withdrawl rat model.We utilized molecular biology and behavioral method to detect the relationship between the expression of PER1 and behavior.Finally,We examine the expression of the Tyrosine hydroxylase(Tyrosine hydroxylase,TH)and dopamine D2 receptor(DRD2)to explore whether PER1 impact drug dependence by the Tyrosine hydroxylase(TH)activity and change the DRD2 reactivity.Methods: 1.Male Sprague-Dawley rats(200~250g)were fed in a 12/12 h light/dark cycle.One group of rats was given 2 weeks alternating intraperitoneal injection with methamphetamine(3mg/kg)or saline(1ml/kg),Another group(n=14)received saline only.After injected with methamphetamine or saline,the rats were placed in the methamphetamine or saline conditioning chambers for 45 min immediately.On day14,Conditional place preference(CPP)was test to confirm rat model of methamphetamine withdrawl.After 10 days' withdrawal,using open-field test to detect the behavior of the rats.Rats were decapitated at ZT4~ZT5.Then detect expression of PER1 of PFC,NAc,Amy and Hip.2.7 days after tereotaxic operation in the PFC and NAc,to establish the methampeta-mine withdrawl rat model.After 10 days' abstinence,using open-field test to detect the behavior of the rats.Then rats were decapitated at ZT4-ZT5 and detected expression of PER1,TH and DRD2 of PFC and NAc.Results: 1.Compared to saline group,the score of CPP of withdrawl group were significantly increased in posttest.(p<0.05).2.The expression of PER1 in PFC,NAc and Amy of withdrawal group were significantlyhigher than the control group(p<0.05),But there were not difference in Hip(p>0.05).3.After AAV-per1 treatment of NAc,Compared to pretest,the score of CPP was significantly decreased in posttest(p<0.05).After AAV-per1 treatment of PFC,Compared to pretest,the score of CPP was not significantly difference in posttest.4.Western blot results showed that the expression of TH and DRD2 of each group has no significantly difference in each group(p>0.05).Conclusion:1.Established the model of methamphetamine withdrawl rat suceussfully.2.The PER1 of NAc and PFC may mediated withdrawal behavior in chronic methamphetamine addiction.3.The TH,DRD2 of NAc and PFC may be indirectly affect the withdrawal behavior in chronic methamphetamine addiction.