食物成瘾是肥胖症发生发展的重要原因，58%重度肥胖与之有关。患者因食物依赖而难以通过自己控制摄食行为而实现减肥。但脑深部电刺激（DBS）伏隔核壳部能够上调壳部D2受体且实现减肥，而D2受体是成瘾产生的主要机制，故我们推测这主要与控制了成瘾性摄食行为有关。故本研究将观察DBS伏隔核壳部对食物成瘾的治疗效果并探索相关机制。本研究利用食物成瘾模型诱导肥胖，探索其在肥胖发生发展过程中的作用，然后对食物成瘾大鼠实施伏隔核壳部DBS观察DBS对成瘾性摄食行为的调控作用，并观探索其治疗机制。本研究利用QRT-PCR、Western-blot检测DBS对摄食奖赏中枢相关神经核团内D2受体、瘦素瘦体及通路蛋白、炎症介质等基因与蛋白表达的影响，利用微透析和高效液相色谱分析技术检测电刺激对相关核团神经递质的影响, 以此探索DBS治疗食物成瘾的相关机制。本研究为肥胖症的治疗提供新的思路和理论依据。

Pertinent to 58% percent of fatally morbid obesity, food addiction to a large extent contributes for the development of obesity. The obese cannot helping ingesting palatable foods on the account of dependence and self-control deficiency for food. However, our previous research found that deep brain stimulation(DBS) of nucleus accumbens shell subregion (Acb-Sh) in rats could treat obesity and upregulate Dopamine receptor DR2 which was considered to be closely related with addictive behaviors. Therefore, we postulate that it should owe the success to the control of addictive digestion behaviors. Considering that, present study will explore the effect of DBS of Acb-Sh for food addiction rats and the potential mechanisms. By observing the process obesity inducing of food addiction rats, present study will explore its mechanisms involved in the development of obesity. Another aim of present study is to observe whether the DBS of Acb-Sh could impede the development of FA via the experiment that induces the obese-prone rats into obesity and meanwhile implement the process of DBS. In order to explore the potential mechanisms involved, present study will carry out Realtime Quantitative PCR (QRT –PCR ), Western-Blot to detect the changes of gene and protein expression of DR2, leptin receptor and its pertinent proteins of leptin receptor activating-pathway, inflammatory mediators , as well as carry out microdialysis and high-performance liquid chromatography (HPLC) to detect the effect of DBS on neurotransmitters in relative necleus. In all, present study will provide a fresh and promising management and rationale for obesity treatments.

食物成瘾是肥胖症发生发展的重要因素，控制食物成瘾成为治疗肥胖症的一个新的思路。本研究首先究利用限制性高脂食物饲养联合彩光刺激的方法可有效建立食物成瘾模型。与对照组小鼠相比，食物成瘾小鼠存在暴饮暴食、强迫进食和焦虑样行为，同时对高脂食物的摄食动机较正常对照组增加。将食物成瘾小鼠和对照组小鼠同时给予高脂饲养，发现食物成瘾小鼠更容易发展为肥胖症。而伏隔核壳部高频电刺激可以有效改善食物成瘾行为，可以降低体重及对高脂食物的摄食动机。在机制研究中我们发现，食物成瘾可能与伏隔核壳部的CRFR1受体的上调和Dopr2的下调有关。而伏隔核壳部高频电刺激可以逆转以上基因的改变。而且我们利用微透析的方法研究伏隔核壳部高频电刺激对摄食相关核团的神经递质的影响。壳部高频电刺激可以使下游神经核团GABA升高，这可能与传出性轴突的直接激活有关，这可能是伏隔核治疗食物成瘾的机制之一。综述可知，伏隔核壳部高频电刺激可以有效降低食物成瘾，其机制可能与激活壳部GABA传出性轴突有关，而且慢性电刺激可以使CRFR1表达下调、Dopr2上调。我们的研究为未来的肥胖症治疗提供了新的思路，并对机制进行了初步探索，为治疗提供了理论依据。