Department of Pharmacotherapeutics, Showa Pharmaceutical University, 3-3165, Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543, Japan.
Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba, 260-8670, Japan.
Pharmacol Rep. 2021 Aug;73(4):984-1003. doi: 10.1007/s43440-021-00246-y. Epub 2021 May 6.
Endocannabinoids are involved in various physiological functions, including synaptic plasticity and memory, and some psychiatric disorders, such as posttraumatic stress disorder (PTSD), through the activation of cannabinoid (CB) receptors. Patients with PTSD often show excessive fear memory and impairment of fear extinction (FE). It has been reported that the stability of acquired fear memory is altered through multiple memory stages, such as consolidation and reconsolidation. FE also affects the stability of fear memory. Each stage of fear memory formation and FE are regulated by different molecular mechanisms, including the CB system. However, to the best of our knowledge, no review summarizes the role of the CB system during each stage of fear memory formation and FE. In this review, we summarize the roles of endocannabinoids in fear memory formation and FE. Moreover, based on the summary, we propose a new hypothesis for the role of endocannabinoids in fear regulation, and discuss treatment for PTSD using CB system-related drugs.
内源性大麻素通过激活大麻素（CB）受体参与各种生理功能，包括突触可塑性和记忆，以及一些精神疾病，如创伤后应激障碍（PTSD）。PTSD 患者常表现出过度的恐惧记忆和恐惧消除（FE）障碍。据报道，获得性恐惧记忆的稳定性通过多个记忆阶段发生改变，如巩固和再巩固。FE 也会影响恐惧记忆的稳定性。恐惧记忆形成和 FE 的每个阶段都受到不同分子机制的调节，包括 CB 系统。然而，据我们所知，尚无综述总结 CB 系统在恐惧记忆形成和 FE 的各个阶段中的作用。在本综述中，我们总结了内源性大麻素在恐惧记忆形成和 FE 中的作用。此外，基于总结，我们提出了内源性大麻素在恐惧调节中的作用的新假设，并讨论了使用 CB 系统相关药物治疗 PTSD。
