内侧前额叶到背内侧纹状体投射的GABAB受体对暴食行为的调控机制研究

暴食行为是一种无法自控的大量进食且心理紊乱的进食障碍特征性行为，常见于神经性贪食与暴食症，两者总发病率高达5.8%，由于反复发作的暴食行为与心理紊乱对患者造成严重的身体与精神损害，然而目前其神经病理机制不清、治疗手段匮乏，是临床亟待解决的重大问题。我们前期研究发现，内侧前额叶到背内侧纹状体的投射异常，可能是暴食行为的重要病理机制，采用巴氯芬干预-激活GABAB受体，显著地抑制暴食行为，据此推测：内侧前额叶GABAB受体可能是重要的调控靶点，内侧前额叶到背内侧纹状体的投射紊乱与其GABAB受体异常诱发暴食行为。为进一步探索该科学问题，我们构建“暴食”动物模型，采用光遗传学、电生理与分子生物学技术，从脑区、环路、神经与靶点分子多层次探究调控暴食行为的神经病理性机制，为进食障碍暴食的临床治疗提供潜在的干预脑区与分子靶点，缓解进食障碍面临的临床困境，具有重要的临床价值与现实意义。

Eating disorders (ED) are characterized by abnormal eating behaviors and psychological disorders, including bulimia nervosa (BN) and binge eating disrobers (BED). BN and BED are characterized binge eating (BE) behaviors, which causes mental and physical harms to the BE-related patients; the incidence rate with BE is up to 5.8% in the general population abroad. However, the major clinical problems are urgent to be solved that its neuropathological mechanism is unclear and treatment methods are scarce. Currently, our previous studies have found that the neurocircuit abnormalities from the medial prefrontal cortex (mPFC) to the dorsal medial striatum (DMS) may be the main neuropathological mechanisms of BE behaviors; the GABAB receptors in the mPFC-DMS projection are disordered, which may induce binge eating behaviors; and treatment of baclofen significantly inhibits the BE-like behaviors. In order to further explore and confirm the relationships between the abnormal changes of GABAB receptors in the mPFC-DMS projection and BE behaviors, and to analyze the neurobiological mechanism of BE behaviors, a BE-like animal model is constructed, by using electrophysiology, optogenetics and molecular biology techniques，to explore the neuropathological mechanisms of brain regions, neural circuits and molecules, and provide effective intervention ways for BE clinical treatment, which is of great value and importance to alleviate the clinical dilemma of ED.