Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.
Pharmacol Biochem Behav. 2012 Feb;100(4):688-704. doi: 10.1016/j.pbb.2011.04.016. Epub 2011 Apr 21.
Accumulating evidence suggests that the glutamatergic system plays important roles in the pathophysiology and treatment of major depressive disorder (MDD). Abnormalities in the glutamatergic system are definitely observed in this disorder, and certain glutamatergic agents exhibit antidepressant effects in patients with MDD. In this review, we summarize the preclinical findings suggesting the involvement of glutamate signaling in the pathophysiology and treatment of MDD. Preclinical animal models for depression are often characterized by changes in molecules related to glutamatergic signaling. Some antidepressants exert their effects by affecting glutamatergic system components in animals. Animals with genetically modified glutamatergic function exhibit depression-like behaviors or anti-depressive behavior. In addition, several types of glutamatergic agents have shown antidepressant-like effects in preclinical models for depression. Many types of glutamate receptors (NMDA, AMPA, and metabotropic glutamate receptors) or transporters appear to be involved in the etiology of depression or in the mechanisms of action of antidepressants. These functional proteins related to glutamate signal transduction are potential targets for a new generation of antidepressants with fast-onset effects, such as the NMDA antagonist ketamine.
越来越多的证据表明，谷氨酸能系统在重性抑郁障碍（MDD）的病理生理学和治疗中发挥重要作用。在这种疾病中肯定观察到谷氨酸能系统的异常，某些谷氨酸能药物在 MDD 患者中表现出抗抑郁作用。在这篇综述中，我们总结了提示谷氨酸信号参与 MDD 病理生理学和治疗的临床前发现。用于抑郁的临床前动物模型通常表现出与谷氨酸能信号相关的分子的变化。一些抗抑郁药通过影响动物的谷氨酸能系统成分发挥作用。具有遗传修饰的谷氨酸能功能的动物表现出抑郁样行为或抗抑郁样行为。此外，几种类型的谷氨酸能药物在抑郁的临床前模型中显示出抗抑郁样作用。许多类型的谷氨酸受体（NMDA、AMPA 和代谢型谷氨酸受体）或转运体似乎参与了抑郁的病因或抗抑郁药的作用机制。这些与谷氨酸信号转导相关的功能性蛋白质可能是新一代具有快速起效作用的抗抑郁药的潜在靶点，例如 NMDA 拮抗剂氯胺酮。
