大脑奖赏环路调控心理性ED患者性快感缺乏的神经生物学机制研究

Erectile dysfunction (ED) is the most common sexual dysfunction in men. However, its etiology is still unclear. Most previous studies have explored organic ED, rarely involved in pED. We have explored the central pathological neurologic mechanism in pED patients and found that the function and structure of the emotion and attentive circuits were abnormal. The reward circuit is one of the most important circuits of the brain. Therefore, we hypothesized that sexual activity mihgt be regulated by the reward loop and its neurotransmitter dopamine (DA). We designed the following experiments: (1) with the method of fMRI, we explore the differences of the reward circuit (orbitofrontal cortex (OFC) - the anterior cingulate cortex (ACC) - ventral tegmental area (VTA)) between ahedonia patients with psychological ED and healthy controls. (2) establishing the ahedonia rata model, and observe the correlation between different brain regions of the the reward circuit, the molecular biological mechanism of DA and other neurotransmitters and the sexual behavior of rats. (3) choosing the brain regions with abnormal function as therapeutic targets and exploring the effect of repetitive transcranial magnetic stimulation (rTMS) on ED and cognition. The purpose is to establish the drugs and physical therapy in the light of abnormal brain regions.

心理性勃起功能障碍（pED）是常见性功能障碍，发病机制不明。既往研究大多从器质性ED入手，pED涉及很少。申请人前一个国基金对pED患者中枢性病理神经机制进行初步探索，发现pED患者大脑情绪环路与注意网络存在功能与结构异常，而大脑奖赏环路是其中最重要一个环路。因此课题组提出假说：性中枢通过奖赏环路及其神经递质多巴胺（DA）发挥性活动调控作用，设计以下实验：（1）伴性快感缺失亚型pED患者与正常对照的眶额皮质（OFC）-前扣带回（ACC）-腹侧背盖区（VTA）奖赏环路的功能磁共振（fMRI）检测和分析；（2）构建伴快感缺失亚型pED大鼠模型，并探索大鼠大脑中枢奖赏环路各核团之间联系、DA等神经递质的分子生物学机制，并观察大鼠性行为效应；（3）挑选功能异常脑区作为治疗靶点，观察重复经颅磁刺激（rTMS）对患者勃起功能与心理动机的治疗效应；以期建立针对异常脑区靶点的药物和物理定位治疗手段。

心理性勃起功能障碍（pED）是常见性功能障碍，发病机制不明。既往研究大多从器质性ED入手，pED涉及很少。申请人前一个国基金对pED患者中枢性病理神经机制进行初步探索，发现pED患者大脑情绪环路与注意网络存在功能与结构异常，而大脑奖赏环路是其中最重要一个环路。本项目主要探索了奖赏环路及其神经递质多巴胺（DA）调控性活动的中枢机制。研究发现：（1）伴性快感缺失pED的发生与患者眶额皮质（OFC）-前扣带回（ACC）-腹侧背盖区（VTA）奖赏环路的功能异常相关；（2）伴快感缺失pED大鼠大脑中枢奖赏环路各核团之间功能联系、DA水平均发生异常，并进一步介导了大鼠性行为的紊乱；（3）挑选功能异常脑区作为治疗靶点，使用重复经颅磁刺激（rTMS）可有效改善患者大脑中奖赏环路功能的异常，同时改善勃起功能与心理动机。此项目为建立针对伴性快感缺失pED异常脑区靶点的药物和物理定位治疗手段提供了理论依据。