Roles of glutamate signaling in preclinical and/or mechanistic models of depression

被引:70
作者
Tokita, Kenichi [1 ,2 ]
Yamaji, Takayuki [2 ]
Hashimoto, Kenji [1 ]
机构
[1] Chiba Univ, Div Clin Neurosci, Ctr Forens Mental Hlth, Chiba 2608670, Japan
[2] Astellas Pharrna Inc, Drug Discovery Res, Appl Pharmacol Res Labs, Tsukuba, Ibaraki 3058585, Japan
关键词
Glutamate; Major depressive disorder; NMDA receptor; AMPA receptor; Metabotropic glutamate receptor; Animal models; FORCED SWIM TEST; ANTIDEPRESSANT-LIKE ACTIONS; D-ASPARTATE ANTAGONIST; CHRONIC MILD STRESS; TREATMENT-RESISTANT DEPRESSION; AMPA RECEPTOR POTENTIATORS; GAMMA-AMINOBUTYRIC-ACID; EXCITATORY AMINO-ACIDS; PROOF-OF-CONCEPT; NMDA RECEPTOR;
D O I
10.1016/j.pbb.2011.04.016
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:688 / 704
页数:17
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