越鞠丸是治疗中医郁证的经典方，其治疗抑郁症作用得到众多临床研究结果支持。我们前期的动物实验与临床研究揭示了越鞠丸还具有快速抗抑郁效果，进一步发现越鞠丸可快速提高抑郁症相关脑区海马腺苷酸环化酶激活肽（PACAP）的表达，并激活PACAP下游CREB信号，且其抗抑郁作用依赖于CREB的激活。在此基础上，我们提出海马PACAP及相关信号通路作为介导越鞠丸快速抗抑郁的分子神经基础的假说。本项目拟采用免疫印迹、颅内微注射PACAP拮抗剂、药理遗传（DREADD）选择性抑制海马PACAP神经元活动等方法，研究越鞠丸快速抗抑郁作用：1. 对海马PACAP表达的依赖性; 2. 与PACAP下游CREB、AKT等通路的相关性；3. PACAP通路引起的突触可塑性变化的相关性。本项目通过研究PACAP在越鞠丸快速抗抑郁中的作用机制，确立PACAP作为新的快速抗抑郁靶点，为扩大越鞠丸临床应用提供科学依据。

Yueju pill is a classic Traditional Chinese Medicine formula which could treat Yu syndrome in TCM. Many results of clinical studies have supported that Yueju pill has an antidepressant effect. Our previous clinical and animal studies demonstrated that Yueju can produce a rapid antidepressant effect. We found Yueju can rapidly increase the expression of PACAP in the hippocampus, the depression-related brain region, and activate the downstream signal CREB on which the antidepressant effect of Yueju is dependent. Therefore, we hypothesize that the up-regulation of PACAP and downstream signaling pathways may induce the rapid antidepressant effect of Yueju. Our project will utilize multiple methods including: western blot, intracranial microinjection PACAP antagonist, Designer Receptor Exclusively Activated by Designer Drugs (DREADD) selectively inhibition on PACAP neuronal activity, etc., to specifically investigate whether the rapid antidepressant efficiency of Yueju, 1. Is dependent on the up-regulated expression of PACAP in the hippocampus; 2.is associated with activation of downstream signaling of PACAP, such as CREB, AKT, etc; 3. Is associated with synaptic plasticity changes induced by PACAP. By studying the role of PACAP in the rapid antidepressant effect of Yueju, we may identify PACAP as a novel target for the rapid antidepressant effect, and provide a scientific basis for the clinical use of Yueju.