The identity of the mechanism by which the Baixiangdan capsule (BXD) and the Shuyu capsule (SY) control anger-out (AO) and anger-in (AI) in rodents is unclear. The current study clarified the intervention role of BXD and SY on AO and AI male rats. We further explored the differences between BXD and SY in the treatment of AO and AI rats. Social isolation combined with the resident-intruder paradigm was used to establish the anger-out and AI rats models. On this basis, GABA content in the dorsal raphe nucleus (DRN) and serotonin (5-HT) contents in these brain regions were detected using ELISA after various time courses (0, 1, 3, 5, and 7 days) treated with BXD and SY. Co-expression of 5-HT and GB1 in the DRN was detected. GB1-specific agonist baclofen and GB1-specific inhibitor CGP35348 were injected into the DRN. Changes in 5-HT levels in these brain regions were then detected. After treatment, rats in the BXD group exhibited lower aggressive behavior scores, longer latencies of aggression, lower total distances in the open field test, and a higher sucrose preference coefficient. Meanwhile, rats in the SY group exhibited higher aggressive behavior scores, shorter latencies of aggression, higher total distances in the open field test, and higher sucrose preference coefficients. With increasing medication duration, 5-HT levels in these brain regions were increased gradually, whereas GABA levels in the DRN were decreased gradually, and all recovered to normal levels by the 7th day. A large number of 5-HT-positive cells could be found in the immunofluorescence section in the DRN containing GABABR1 (GB1)-positive cells, indicating that 5-HT neurons in the DRN co-expressed with GB1. Furthermore, after the drug intervention, the 5-HT level in the DRN was elevated to a normal level, and the GB1 level in the DRN was decreased to a normal level. After the microinjection of baclofen into the DRN, the 5-HT contents in these brain regions were decreased. By contrast, the 5-HT contents were increased after injection with CGP35348. BXD and SY could effectively improve the abnormal behavior changes of AO and AI rats, and the optimal duration of action was 7 days. The improvement way is as follows: Decreased abnormal increase of GABA and GB1 in the DRN further mediated synaptic inhibition and increased 5-HT level in the DRN, leading to increased 5-HT levels in the PFC, hypothalamus, and hippocampus. Therefore, GB1-mediated GABA in the DRN could regulate 5-HT levels in these brain regions, which may be one of the ways by which BXD and SY treat AO and AI, respectively.

中文翻译：

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白香丹胶囊和舒郁胶囊分别调节愤怒和愤怒：GB1 介导的 GABA 可以调节多个脑区的 5-HT 水平

白香丹胶囊 (BXD) 和舒郁胶囊 (SY) 控制啮齿动物愤怒 (AO) 和愤怒 (AI) 的机制尚不清楚。目前的研究阐明了BXD和SY对AO和AI雄性大鼠的干预作用。我们进一步探讨了 BXD 和 SY 在治疗 AO 和 AI 大鼠方面的差异。社会隔离与常驻入侵者范式相结合，用于建立愤怒和 AI 大鼠模型。在此基础上，采用ELISA法检测BXD处理不同时程（0、1、3、5、7天）后这些脑区中缝背核（DRN）中的GABA含量和5-羟色胺（5-HT）含量和SY。检测到 5-HT 和 GB1 在 DRN 中的共表达。将 GB1 特异性激动剂巴氯芬和 GB1 特异性抑制剂 CGP35348 注射到 DRN 中。然后检测到这些大脑区域中 5-HT 水平的变化。治疗后，BXD组大鼠表现出较低的攻击行为评分、较长的攻击潜伏期、较短的旷场测试总距离和较高的蔗糖偏好系数。同时，SY组大鼠表现出更高的攻击行为评分、更短的攻击潜伏期、更高的旷场总距离和更高的蔗糖偏好系数。随着服药时间的延长，这些脑区的5-HT水平逐渐升高，而DRN中的GABA水平逐渐降低，至第7天均恢复至正常水平。在含有 GABABR1 (GB1) 阳性细胞的 DRN 的免疫荧光切片中可以发现大量 5-HT 阳性细胞，表明 DRN 中的 5-HT 神经元与 GB1 共表达。此外，药物干预后DRN中5-HT水平升高至正常水平，DRN中GB1水平降低至正常水平。将巴氯芬显微注射到 DRN 后，这些脑区的 5-HT 含量降低。相比之下，注射 CGP35348 后 5-HT 含量增加。BXD和SY能有效改善AO和AI大鼠的异常行为改变，最佳作用时间为7天。改善途径如下：减少DRN中GABA和GB1的异常增加，进一步介导突触抑制，增加DRN中5-HT水平，导致PFC、下丘脑和海马5-HT水平升高。所以，