The Effect Of Berberine On Morphine And Cocaine Addiction And Its Mechanism

Objective: Drug addiction has become a global problem that seriously threatens human health and social stability.The core problem of drug addiction treatment is the high relapse rate after withdrawal.Drug addiction memory and the incubation of drug craving caused relapse.Studies have found that berberine has a neuroprotective effect on neurodegenerative diseases such as Alzheimer's disease.This study will observe the effect of different doses berberine on extinction and priming in morphine induced conditioned place preference(CPP),to evaluate the effect of berberine on morphine addition;in rat jugular vein self-administration model confirmed the effect of berberine on drug addiction relapse;use Western blot to detection the expression of RPS6 protein on 1day and 10 day in rat prefrontal cortex.To explore the role of mammalian rapamycin target protein(mTOR)in cocaine addiction.This experiment will study whether berberine can affect the memory of drug addiction,reduce the craving for drugs,and prevent relapse behavior.Methods:1 Morphine(10 mg/kg,i.p)was injected before each programmed training for seven days to build the mice model of CPP.After CPP test,the 7 days' extinction procedure with different doses berberine(10,25,50mg/kg,i.g),observe the effect of berberine on extinction.Then,5 mg/kg morphine was admistered before the priming test.2 We trained rats to self-administer cocaine with FR1 procedure.Berberine(20 mg/kg,i.p)was given to observe the effect of berberine on the extinction of drug memory.Then,5 mg/kg cocaine was admistered before the priming test.3 Assessed the effect of berberine(20 mg/kg,i.p)on spontaneous recovery of cocaine seeking in a rat model of drug relapse.4 With Western blot,we observed the protein levels of p-rps6 in mPFC after berberine treatment for 1day and 10 day in cocaine self-administration model.Results:1.The role of berberine in extinction and priming on morphine CPP:(1)25 mg/kg and 50 mg/kg berberine enhanced the extinction process in CPP(2)25 mg/kg and 50 mg/kg berberine could significantly inhibit the CPP priming caused by small doses of morphine,and the effect of 10 mg/kg group was not obvious.2.The role of berberine in extinction and priming on cocaine SA in rats: Berberine significantly promoted the extinction process compared with the control group;20 mg/kg berberine could significantly inhibit the priming of small doses of cocaine.3.Berberine inhibit the spontaneous recovery of cocaine.4.Berberine increased the expression of p-rps6 but not rps6 in mPFC.Conclusions:1.Berberine could promote the extinction of drug addiction,inhibit the priming of small doses of morphine and cocaine,and reduce the relaps behavior.2.Berberine could promote the extinction of drug addiction,inhibit the expression of drug addiction memory.3.Berberine inhibits drug craving is associated with mTOR signaling pathway.