Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Institute of Neurophysiopathology, INP, CNRS, Aix-Marseille University, 13005 Marseille, France.
Curr Neuropharmacol. 2024;22(5):916-934. doi: 10.2174/1570159X21666230803101629.
Neurotensin (NT) is a 13-amino acid neuropeptide widely distributed in the CNS that has been involved in the pathophysiology of many neural and psychiatric disorders. There are three known neurotensin receptors (NTSRs), which mediate multiple actions, and form the neurotensinergic system in conjunction with NT. NTSR1 is the main mediator of NT, displaying effects in both the CNS and the periphery, while NTSR2 is mainly expressed in the brain and NTSR3 has a broader expression pattern. In this review, we bring together up-to-date studies showing an involvement of the neurotensinergic system in different aspects of the stress response and the main stress-related disorders, such as depression and anxiety, post-traumatic stress disorder (PTSD) and its associated symptoms, such as fear memory and maternal separation, ethanol addiction, and substance abuse. Emphasis is put on gene, mRNA, and protein alterations of NT and NTSRs, as well as behavioral and pharmacological studies, leading to evidence-based suggestions on the implicated regulating mechanisms as well as their therapeutic exploitation. Stress responses and anxiety involve mainly NTSR1, but also NTSR2 and NTSR3. NTSR1 and NTSR3 are primarily implicated in depression, while NTSR2 and secondarily NTSR1 in PTSD. NTSR1 is interrelated with substance and drug abuse and NTSR2 with fear memory, while all NTSRs seem to be implicated in ethanol consumption. Some of the actions of NT and NTSRs in these pathological settings may be driven through interactions between NT and corticotrophin releasing factor (CRF) in their regulatory contribution, as well as by NT's pro-inflammatory mediating actions.
神经降压素（NT）是一种广泛分布于中枢神经系统的 13 个氨基酸神经肽，已参与多种神经和精神疾病的病理生理学过程。有三种已知的神经降压素受体（NTSR），它们介导多种作用，并与 NT 一起形成神经降压素能系统。NTSR1 是 NT 的主要介导者，在中枢神经系统和外周均显示出作用，而 NTSR2 主要在大脑中表达，NTSR3 则具有更广泛的表达模式。在这篇综述中，我们汇集了最新的研究，表明神经降压素能系统参与了应激反应的不同方面，以及主要的与应激相关的疾病，如抑郁和焦虑、创伤后应激障碍（PTSD）及其相关症状，如恐惧记忆和母婴分离、乙醇成瘾和物质滥用。重点介绍了 NT 和 NTSR 的基因、mRNA 和蛋白质改变，以及行为和药理学研究，为涉及的调节机制及其治疗开发提供了基于证据的建议。应激反应和焦虑主要涉及 NTSR1，但也涉及 NTSR2 和 NTSR3。NTSR1 主要与抑郁有关，而 NTSR2 主要与 PTSD 有关，其次是 NTSR1。NTSR1 与物质和药物滥用有关，NTSR2 与恐惧记忆有关，而所有 NTSR 似乎都与乙醇消耗有关。在这些病理情况下，NT 和 NTSR 的一些作用可能是通过其调节作用中 NT 与促肾上腺皮质释放因子（CRF）之间的相互作用以及 NT 的促炎介导作用驱动的。
