ΔFosB Expression After Deep Brain Stimulus To The Nuclear Accumbens On Morphine Dependence In Rats And Probe Into Depressive Behavior After Drug Withdrawal

Surgical ablation of select brain areas has been frequently used to alleviatepsychological dependence on opiate drugs in certain countries. However, ablative brainsurgery was stopped in China in2004due to the related ethical controversy and possibleside effects. Deep brain stimulation (DBS), a less invasive, reversible and adjustableprocess of neuromodulation, was adopted to attenuate relapses in studies of drug addiction.And opioid-dependent patients are often prone to anxiety, irritability, depression and otheremotions, this kind of negative emotions is also the key factors which lead to relapse. Theoccurrence of depression and chronic drug addiction has a high degree of correlation inneural anatomy and neurobiology, the spontaneous drug-seeking behavior established by self-administration system of rats can be more accurately simulate human spontaneousdrug seeking and relapse, which pave the way to study the mechanisms of drug addictionand depression-like behavior after drug withdrawal.Objective To observe the behaviors of drug self-administration rats after morphinewithdrawal, evaluate the depressive-like behaviors after drug withdrawal and discuss theestablishment of depression rat model. And do the implementation of the bilateralNAc-DBS surgery on morphine-addiction rats. Then the change of ΔFosB expression inNAc was analyzed, which provide molecular evidence for the NAc-DBS in the treatmentof drug dependence.Methods1.18adult rats weighing240–260g were divided into three groups, which included aDBS group (n=6, administration of surgery, morphine and DBS), a sham DBS group (n=6, administration of surgery and morphine) and a control group (n=6, administration ofphysiological saline).2.16SD rats were chosen and randomly divided into drug self-administrationgroup(model group) and saline treatment group(NS group).Construct the chronicintravenous catheter for all16rats.Establish morphine self-administration model onmodel group(8rats),and then relapse. Their behaviors with Gellert-Hohzman method onthe third day after withdrawal in the following tests: open field test, sucrose preference test,the test of body weight and diet amount changes and the coefficient of brain wereobserved.Results1.The bilateral NAc DBS attenuated morphine-induced reinstatement of drug seeking.Subsequent immunohistochemistry measurements revealed that the behavioralconsequences were associated with a significant reduction in the expression of ΔFosB inthe NAc.2. In the period of withdrawal after relapse, body weight and diet amount, thecoefficient of brain, open field tests scores, sucrose consumption and the sucrosepreference（P＜0.05） decreased. Conclusion1. These findings indicate that the NAc DBS could be an effective and safetherapeutic option for preventing relapse to morphine addiction.2. In the period of withdrawal after relapse, withdrawal symptoms of morphineself-administration rats which lead to the depressive-like behaviors are significant. In viewof the similarity with human addiction relapse behavior, drug self-administration modelcan be used as depression experimental model.