早泄是男性最常见的性功能障碍疾病之一，能显著降低患者性生活质量和满意度，严重影响夫妻之间感情，甚至导致婚姻家庭的破裂。近年来，临床研究发现Tramadol能明显延长患者阴道内射精潜伏期，提高患者性生活满意度，可作为超说明书（off-label）的药物治疗早泄，但具体作用机制不明。本课题组的前期研究结果发现，下丘脑室旁核（PVN）在调节生理性射精行为方面发挥着重要作用。我们设想Tramadol主要作用于PVN谷氨酸能神经元参与射精行为的调控。围绕这一假说，本项目拟从动物行为学、神经环路、细胞和分子水平，采用行为学、神经药理学、电生理学、免疫荧光组织化学和分子生物学技术，综合观察和分析Tramadol对PVN谷氨酸能神经元活动作用及其介导的射精行为的影响。研究结果将阐明Tramadol药物治疗早泄的中枢作用机制，同时也将为临床应用高选择性阿片类药物治疗早泄提供理论依据。

Premature ejaculation is one of the most common sexual dysfunction diseases in men, which significantly reduces the quality of life and satisfaction of patients, seriously affects the relationship between husband and wife, and even leads to the breakdown of marriage and family. In recent years, Tramadol has been found to significantly prolong the vaginal ejaculation latency and improve the patient's sexual life satisfaction. It can be used as an off-label drug to treat premature ejaculation, but the specific mechanism is unknown. In the previous study, we have demonstrated that hypothalamic paraventricular nucleus (PVN) plays an important role in the physiological regulation of ejaculation behavior. We hypothesize that Tramadol influences ejaculation through acting on PVN glutamatergic neurons. To test our hypothesis, we intend to comprehensively observe and analyze the mechanisms of Tramadol in mediating ejaculation from animal behavior, neural circuits, cell and molecular levels, using behavioral, neuropharmacology, electrophysiology, immunofluorescence histochemistry and molecular biology techniques. The results will shed light on the central mechanism of clinical treatment of premature ejaculation with Tramadol, as well as clinically useful clues for the use of highly selective opioids for premature ejaculation treatment.