Effects Of Bilateral Nucleus Accumbens Lesions On Morphine-induced Reactivation Of Extinguished Conditioned Place Preference

Background and aim: Chronic vulnerability to relapse is a formidable challenge for the treatment of drug addiction. The mesolimbic dopaminergic system plays an important role in drug-triggered relapse. Ablation of related nucleus in this system such as nucleus accumbens may be a potential treatment to drug addiction. To perform more research in this field, reliable animal model is necessary. The conditioned place preference animal model is in common use in addiction research, which is also employed in research on relapse as"reactivation". According to different literatures, conditioned place preference persisted for different times after it was obtained by training with morphine. One possible explanation for this is the different characters of boxes, such as two chambers versus three chambers. Furthermore, it has been reported that lesions of bilateral of NAc can abolish morphine-triggered reactivation. But in those experiments, drug-priming was given at the first days after the lesions, without chronic observation of the effects. This is not consistent with clinic practice, as the detoxed addict can be triggered to relapse at any time after detoxification. In our research, we investigated whether CPP scores measured by 2-chambers box were different with 3-chambers box and established the reactivation model. The chronic influence of bilateral NAc lesions on drug-priming relapse was also observed.Method: Firstly, conditioned place preference model was set up in rats. The rats were trained to associate white chamber with morphine. After training for 6 days, the CPP scores were measured by 2 and 3-chambers boxes. Secondly, the reactivation model was established according to foregoing experiment. Lastly, the effects of bilateral nucleus accumbens lesions on morphine-induced reactivation of extinguished conditioned place preference were investigated. Subject was divided into lesion, sham and control groups (n=10). Morphine was administered via subcutaneous injection at 10mg/kg for 6 days to establish conditioned place preference (CPP). From then on, the rats were administered with saline instead of morphine for 5 days to induce CPP extinction. Bilateral NAc was destroyed with direct current(10mA,30s) subsequently. At 3, 10 and 30 days after the ablation, rats were provided with drug priming and the reactivation of extinguished CPP was measured.Result:(1). The average CPP scores after training were significantly higher than scores before training. The average CPP hadn't declined in 15 days after training.(2). Difference of CPP scores measured by 2 or 3 chambers had no statistic significant.(3). The reactivation CPP scores of lesion group were lower than those of sham group at each time point when drug priming was provided (P<0.05).Conclusion:(1). CPP scores measured by 2-chambers boxes aren't different with those measured by 3-chambers boxes. Conditioned place preference obtained by training can persist for 15 days at least. So in the reactivation model, all CPP scores are measured by 2-chambers box and the CPP is extinguished by anti-training with saline. (2). The inhibition of reactivation by lesions of bilateral NAc reflects suppression of human drug-carving by NAc ablation. Lesions of bilateral NAc can abolish reactivation of extinguished CPP for at least 30 days. The bilateral NAc ablation can prevent relapse for a long time probably.