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Although major depressive disorder (MDD) has caused severe mental harm to overwhelming amounts of patients, the pathogenesis of MDD remains to be studied. Due to the in-depth discussion of the mechanism of new antidepressants like ketamine, the habenula (Hb) was reported to be significant in the onset of MDD and the antidepressant mechanism. In the Hb of depressive-like rodents, various molecular mechanisms and neuronal electrical activities have been reported, but neurotransmitters disorder in response to stress are still unclear. Thus, we divided stress-susceptible and stress-resilient rats after exposure to chronic unpredictable mild stress (CUMS). Multiple metabolites in the Hb were determined by liquid chromatography-tandem mass spectrometry. Based on this approach, we found that glutamate was significantly increased in susceptible group and resilient group, while dopamine was significant decreased in two groups. Gamma-aminobutyric acid was significantly upregulated in susceptible group but downregulated in resilient group. Our study firstly provides quantitative evidence regarding alterations of main neurotransmitters in the Hb of CUMS rats, showing the different role of neurotransmitters in stress susceptibility and stress resilience. Copyright © 2020 Elsevier Inc. All rights reserved.


Yu Tian, Zhonghao Wu, Yue Wang, Chong Chen, Yong He, Tianlan Lan, Yan Li, Mengge Bai, Heming Yu, Xiangyu Chen, Zhi Chen, Ke Cheng, Peng Xie. Alterations of neurotransmitters and related metabolites in the habenula from CUMS-susceptible and -resilient rats. Biochemical and biophysical research communications. 2021 Jan 01;534:422-428

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PMID: 33246560

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