Post-traumatic stress disorder (PTSD) is a common anxiety mental disorder and can be manifested after exposure to a real or perceived life-threatening event. Increased noradrenaline and adrenaline in plasma and urine have been documented in PTSD. Dopamine-β-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and consequently, DBH inhibition reduces catecholamines. Our aim was to evaluate if nepicastat treatment decreases PTSD signs in an animal model. Wild-type (129x1/SvJ) female mice were submitted to PTSD induction protocol. DBH-inhibitor nepicastat (30 mg/kg) or vehicle (0.2% HPMC) were administered once daily since day 0 until day 7 or 12. The percentage of freezing was calculated on days 0, 1, 2, and 7, and behavioral tests were performed. Quantification of nepicastat in plasma and DBH activity in the adrenal gland was evaluated. Catecholamines were quantified by HPLC with electrochemical detection. mRNA expression of Npas4 and Bdnf in hippocampus was evaluated by qPCR.Mice in the PTSD-group and treated with nepicastat showed a decrease in freezing, and an increase in the time spent and entries in open arms in elevated plus maze test. In mice treated with nepicastat, adrenal gland DBH activity was decreased, and catecholamines were also decreased in plasma and tissues. On day 7, in mice treated with nepicastat, there was an increase of Npas4 and Bdnf mRNA expression in the hippocampus.In conclusion, DBH inhibitor nepicastat has an effect consistent with a decrease in the persistence of traumatic memories and anxiety-like behavior in this PTSD mice model. The disruption of traumatic memories through interference with the formation, consolidation, retrieval, and/or expression processes may be important to decrease PTSD symptoms and signs. The increase in Npas4 and Bdnf mRNA expression in the hippocampus may be important to develop a weaker traumatic contextual memory after nepicastat treatment.

创伤后应激障碍（PTSD）是一种常见的焦虑性精神障碍，可以在暴露于真实或感知到的危及生命的事件后表现出来。血浆和尿液中去甲肾上腺素和肾上腺素增加已被记录在 PTSD 中。多巴胺-β-羟化酶 (DBH) 催化多巴胺转化为去甲肾上腺素，因此抑制 DBH 会减少儿茶酚胺。我们的目的是评估 nepicastat 治疗是否能减少动物模型中的 PTSD 体征。野生型 (129x1/SvJ) 雌性小鼠接受 PTSD 诱导方案。DBH 抑制剂 nepicastat (30 mg/kg) 或载体 (0.2% HPMC) 从第 0 天到第 7 天或第 12 天每天给药一次。 在第 0、1、2 和 7 天计算冻结百分比，并进行行为测试进行了。评估了血浆中内匹司他的定量和肾上腺中的 DBH 活性。儿茶酚胺通过 HPLC 与电化学检测进行定量。mRNA表达Npas4 和 北斗通过 qPCR 评估了海马体中的 在用内匹司他治疗的小鼠中，肾上腺 DBH 活性降低，血浆和组织中的儿茶酚胺也降低。在第 7 天，在用 nepicastat 治疗的小鼠中，增加了Npas4 和 北斗海马体中的 mRNA 表达。总而言之，DBH 抑制剂 nepicastat 的作用与该 PTSD 小鼠模型中创伤性记忆和焦虑样行为的持久性降低一致。通过干扰形成、巩固、检索和/或表达过程来破坏创伤记忆对于减少 PTSD 症状和体征可能很重要。的增加Npas4 和 北斗 海马体中的 mRNA 表达对于在 nepicastat 治疗后形成较弱的创伤背景记忆可能很重要。