Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China.
Medical School of Chinese PLA, Beijing, 100853, China.
Mol Neurobiol. 2023 Jul;60(7):3708-3723. doi: 10.1007/s12035-023-03312-z. Epub 2023 Mar 18.
Posttraumatic stress disorder (PTSD) is a neuropsychiatric disease closely related to life-threatening events and psychological stress. Re-experiencing, hyperarousal, avoidance, and numbness are the hallmark symptoms of PTSD, but their underlying neurological processes have not been clearly elucidated. Therefore, the identification and development of drugs for PTSD that targets brain neuronal activities have stalled. Considering that the persistent fear memory induced by traumatic stimulation causes high alertness, high arousal, and cognitive impairment of PTSD symptoms. While the midbrain dopamine system can affect physiological processes such as aversive fear memory learning, consolidation, persistence, and extinction, by altering the functions of the dopaminergic neurons, our viewpoint is that the dopamine system plays a considerable role in the PTSD occurrence and acts as a potential therapeutic target of the disorder. This paper reviews recent findings on the structural and functional connections between ventral tegmental area neurons and the core synaptic circuits involved in PTSD, gene polymorphisms related to the dopamine system that confer susceptibility to clinical PTSD. Moreover, the progress of research on medications that target the dopamine system as PTSD therapies is also discussed. Our goal is to offer some hints for early detection and assist in identifying novel, efficient approaches for treating PTSD.
创伤后应激障碍(PTSD)是一种与危及生命事件和心理压力密切相关的神经精神疾病。再体验、高度警觉、回避和麻木是 PTSD 的标志性症状,但它们的潜在神经过程尚未得到明确阐明。因此,针对大脑神经元活动的 PTSD 药物的识别和开发已经停滞不前。考虑到创伤性刺激引起的持续恐惧记忆会导致 PTSD 症状的高度警觉、高度唤醒和认知障碍。而中脑多巴胺系统可以通过改变多巴胺能神经元的功能来影响厌恶恐惧记忆学习、巩固、持续和消除等生理过程,我们的观点是,多巴胺系统在 PTSD 的发生中起着相当大的作用,并作为该疾病的潜在治疗靶点。本文综述了最近关于腹侧被盖区神经元与 PTSD 相关的核心突触回路之间的结构和功能连接、与临床 PTSD 易感性相关的多巴胺系统基因多态性的研究发现,此外,还讨论了针对多巴胺系统作为 PTSD 治疗药物的研究进展。我们的目标是为早期检测提供一些线索,并有助于确定治疗 PTSD 的新的、有效的方法。