The classic gut hormone cholecystokinin (CCK) and its CCK₂-receptor are expressed in almost all regions of the brain. This widespread expression makes CCK by far the most abundant peptidergic transmitter system in the brain. This CNS-ubiquity has, however, complicated the delineation of the roles of CCK peptides in normal brain functions and neuropsychiatric diseases. Nevertheless, the common panic disorder disease is apparently associated with CCK in the brain. Thus, the C-terminal tetrapeptide fragment of CCK (CCK-4) induces, by intravenous administration in a dose-related manner, panic attacks that are similar to the endogenous attacks in panic disorder patients. This review describes the history behind the discovery of the panicogenic effect of CCK-4. Subsequently, the review discusses three unsettled questions about the involvement of cerebral CCK in the pathogenesis of anxiety and panic disorder, including therapeutic attempts with CCK₂-receptor antagonists.

中文翻译：

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胆囊收缩素和恐慌症：对历史的反思和一些未解决的问题


经典的肠道激素胆囊收缩素 (CCK) 及其 CCK ₂受体在大脑的几乎所有区域都有表达。这种广泛的表达使 CCK 成为迄今为止大脑中最丰富的肽能递质系统。然而，这种中枢神经系统的普遍存在使得 CCK 肽在正常脑功能和神经精神疾病中的作用的描述变得复杂。然而，常见的恐慌症显然与大脑中的 CCK 有关。因此，CCK的C端四肽片段(CCK-4)通过以剂量相关的方式静脉内给药，诱导恐慌发作，这与恐慌症患者的内源性发作相似。这篇综述描述了 CCK-4 引起恐慌效应的发现背后的历史。随后，该综述讨论了关于脑 CCK 参与焦虑和惊恐障碍发病机制的三个尚未解决的问题，包括 CCK ₂受体拮抗剂的治疗尝试。