Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, increased reactivity to unpredictable versus predictable threat signals, deficits in fear extinction, and an inability to discriminate between threat and safety. First-line pharmacotherapies for psychiatric disorders have limited therapeutic efficacy in PTSD. However, recent studies have advanced our understanding of the roles of several limbic neuropeptides in the regulation of defensive behaviors and in the neural processes that are disrupted in PTSD. For example, preclinical studies have shown that blockers of tachykinin pathways, such as the Tac2 pathway, attenuate fear memory consolidation in mice and thus might have unique potential as early post-trauma interventions to prevent PTSD development. Targeting this pathway might also be beneficial in regulating other symptoms of PTSD, including trauma-induced aggressive behavior. In addition, preclinical and clinical studies have shown the important role of angiotensin receptors in fear extinction and the promise of using angiotensin II receptor blockade to reduce PTSD symptom severity. Additional preclinical studies have demonstrated that the oxytocin receptors foster accurate fear discrimination by facilitating fear responses to predictable versus unpredictable threats. Complementary human imaging studies demonstrate unique neural targets of intranasal oxytocin and compare its efficacy with well-established anxiolytic treatments. Finally, promising data from human subjects have demonstrated that a selective vasopressin 1A receptor antagonist reduces anxiety induced by unpredictable threats. This review highlights these novel promising targets for the treatment of unique core elements of PTSD pathophysiology.

创伤后应激障碍 (PTSD) 的特征是高度警觉、对不可预测与可预测威胁信号的反应性增加、恐惧消失的缺陷以及无法区分威胁和安全。精神疾病的一线药物疗法对 PTSD 的治疗效果有限。然而，最近的研究增进了我们对几种边缘神经肽在调节防御行为和在 PTSD 中被破坏的神经过程中的作用的理解。例如，临床前研究表明，速激肽通路的阻滞剂，如 Tac2 通路，可以减弱小鼠的恐惧记忆巩固，因此可能具有独特的潜力作为早期创伤后干预措施，以防止 PTSD 的发展。针对这一途径也可能有益于调节 PTSD 的其他症状，包括创伤引起的攻击行为。此外，临床前和临床研究表明血管紧张素受体在恐惧消退中的重要作用以及使用血管紧张素 II 受体阻断剂降低 PTSD 症状严重程度的前景。其他临床前研究表明，催产素受体通过促进对可预测与不可预测威胁的恐惧反应来促进准确的恐惧区分。补充人体成像研究证明了鼻内催产素的独特神经靶点，并将其功效与成熟的抗焦虑治疗进行了比较。最后，来自人类受试者的有希望的数据表明，选择性加压素 1A 受体拮抗剂可减少由不可预测的威胁引起的焦虑。