The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50-60% have been reported to have progression of gut diseases. In the last two decades, researchers introduced incipient physiological roles for serotonin (5-HT) receptors (5-HTRs), suggesting their importance as a potential pharmacological target in various psychiatric and gut diseases. A growing body of evidence suggests that 5-HT systems affect the brain-gut axis in depressive patients, which leads to gut comorbidity. Recently, preclinical trials of 5-HT4R agonists and antagonists were promising as antipsychotic and prokinetic agents. In the current review, we address the possible pharmacological role and contribution of 5-HT4R in the pathophysiology of chronic depression and associated gut abnormalities. Physiologically, during depression episodes, centers of the sympathetic and parasympathetic nervous system couple together with neuroendocrine systems to alter the function of hypothalamic-pituitary-adrenal (HPA) axis and enteric nervous system (ENS), which in turn leads to onset of gastrointestinal tract (GIT) disorders. Consecutively, the ENS governs a broad spectrum of physiological activities of gut, such as visceral pain and motility. During the stages of emotional stress, hyperactivity of the HPA axis alters the ENS response to physiological and noxious stimuli. Consecutively, stress-induced flare, swelling, hyperalgesia and altered reflexes in gut eventually lead to GIT disorders. In summary, the current review provides prospective information about the role and mechanism of 5-HT4R-based therapeutics for the treatment of depressive disorder and possible consequences for the gut via brain-gut axis interactions. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

中文翻译：

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血清素4受体治疗肠道慢性抑郁症及其相关合并症的潜力。

世界卫生组织的最新估计表明，有超过4.5亿人患有抑郁症和其他精神疾病。在这些中，据报道有50-60％患有肠道疾病。在过去的二十年中，研究人员介绍了5-羟色胺（5-HT）受体（5-HTR）的初期生理作用，表明它们作为各种精神疾病和肠道疾病的潜在药理学目标的重要性。越来越多的证据表明，5-HT系统会影响抑郁症患者的脑肠轴，从而导致肠道合并症。最近，5-HT4R激动剂和拮抗剂的临床前试验有望用作抗精神病药和促动力药。在目前的评论中，我们探讨了5-HT4R在慢性抑郁症和相关肠道异常的病理生理中可能的药理作用和贡献。从生理上讲，在抑郁发作期间，交感神经和副交感神经系统的中心与神经内分泌系统结合在一起，改变下丘脑-垂体-肾上腺（HPA）轴和肠神经系统（ENS）的功能，进而导致胃肠道发作（GIT）疾病。ENS连续控制着肠道的各种生理活动，例如内脏疼痛和运动。在情绪紧张的阶段，HPA轴的过度活跃会改变ENS对生理和有害刺激的反应。压力诱发的耀斑，肿胀，痛觉过敏和肠道反射改变最终导致GIT紊乱。综上所述，本篇综述提供了有关基于5-HT4R的疗法在治疗抑郁症中的作用和机制的前瞻性信息，以及通过脑肠轴相互作用可能对肠道造成的后果。本文是名为“ 5-羟色胺研究：交叉标度和边界”的特刊的一部分。