Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats
Major depressive disorder (MDD) is a serious mental disorder that affects many people. The neurotransmitter deficiency hypothesis has been the crux of much research on the treatment of depression. Anhedonia, as a core symptom, was closely associated with altered levels of 5-hydroxytryptamine (5-HT),...
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Frontiers Media S.A.
2022-04-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.862683/full |
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author | Yan Li Yan Li Zhi Chen Zhi Chen Jianting Zhao Heming Yu Heming Yu Xiangyu Chen Xiangyu Chen Yong He Yu Tian Yue Wang Chong Chen Ke Cheng Ke Cheng Peng Xie Peng Xie |
author_facet | Yan Li Yan Li Zhi Chen Zhi Chen Jianting Zhao Heming Yu Heming Yu Xiangyu Chen Xiangyu Chen Yong He Yu Tian Yue Wang Chong Chen Ke Cheng Ke Cheng Peng Xie Peng Xie |
author_sort | Yan Li |
collection | DOAJ |
description | Major depressive disorder (MDD) is a serious mental disorder that affects many people. The neurotransmitter deficiency hypothesis has been the crux of much research on the treatment of depression. Anhedonia, as a core symptom, was closely associated with altered levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and diverse types of glutamate (Glu) receptors in the nucleus accumbens (NAc). However, there were no reports showing how Glu changed in the NAc, and there were other unreported molecules involved in modulating stress-induced anhedonia. Thus, we investigated changes in neurotransmitters and their related metabolites in GABAergic, serotonergic and catecholaminergic pathways in the NAc of a rat model of chronic unpredictable mild stress- (CUMS-) induced anhedonia-like behavior. Then, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to detect target neurotransmitters and related metabolites in the NAc. Finally, the Western blot was used to assess the expression of key enzymes and receptors. Here, we found that the 5-HT level in anhedonia-susceptible (Sus) rats was increased while the Glu level decreased. DA did not show a significant change among CUMS rats. Correspondingly, we detected a reduction in monoamine oxidase-A (MAOA) and Glu receptor 1 levels in anhedonia-Sus rats while Glu receptor 2 (GluR2) and NMDA2B levels were increased in anhedonia-resilient (Res) rats. We also found that the levels of glutamine (Gln), kynurenic acid (Kya), histamine (HA), L-phenylalanine (L-Phe), and tyramine (Tyra) were changed after CUMS. These alterations in neurotransmitters may serve as a new insight into understanding the development of anhedonia-like behavior in depression. |
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spelling | doaj.art-a4cf6c5443d340f4884043a892cd324c2022-12-22T02:55:29ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-04-011610.3389/fnbeh.2022.862683862683Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like RatsYan Li0Yan Li1Zhi Chen2Zhi Chen3Jianting Zhao4Heming Yu5Heming Yu6Xiangyu Chen7Xiangyu Chen8Yong He9Yu Tian10Yue Wang11Chong Chen12Ke Cheng13Ke Cheng14Peng Xie15Peng Xie16Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical College, Xinxiang, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, Chongqing Medical University, Chongqing, ChinaMajor depressive disorder (MDD) is a serious mental disorder that affects many people. The neurotransmitter deficiency hypothesis has been the crux of much research on the treatment of depression. Anhedonia, as a core symptom, was closely associated with altered levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and diverse types of glutamate (Glu) receptors in the nucleus accumbens (NAc). However, there were no reports showing how Glu changed in the NAc, and there were other unreported molecules involved in modulating stress-induced anhedonia. Thus, we investigated changes in neurotransmitters and their related metabolites in GABAergic, serotonergic and catecholaminergic pathways in the NAc of a rat model of chronic unpredictable mild stress- (CUMS-) induced anhedonia-like behavior. Then, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to detect target neurotransmitters and related metabolites in the NAc. Finally, the Western blot was used to assess the expression of key enzymes and receptors. Here, we found that the 5-HT level in anhedonia-susceptible (Sus) rats was increased while the Glu level decreased. DA did not show a significant change among CUMS rats. Correspondingly, we detected a reduction in monoamine oxidase-A (MAOA) and Glu receptor 1 levels in anhedonia-Sus rats while Glu receptor 2 (GluR2) and NMDA2B levels were increased in anhedonia-resilient (Res) rats. We also found that the levels of glutamine (Gln), kynurenic acid (Kya), histamine (HA), L-phenylalanine (L-Phe), and tyramine (Tyra) were changed after CUMS. These alterations in neurotransmitters may serve as a new insight into understanding the development of anhedonia-like behavior in depression.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.862683/fullmajor depressive disorderchronic unpredictable mild stressnucleus accumbensneurotransmitter5-HTglutamate |
spellingShingle | Yan Li Yan Li Zhi Chen Zhi Chen Jianting Zhao Heming Yu Heming Yu Xiangyu Chen Xiangyu Chen Yong He Yu Tian Yue Wang Chong Chen Ke Cheng Ke Cheng Peng Xie Peng Xie Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats Frontiers in Behavioral Neuroscience major depressive disorder chronic unpredictable mild stress nucleus accumbens neurotransmitter 5-HT glutamate |
title | Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats |
title_full | Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats |
title_fullStr | Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats |
title_full_unstemmed | Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats |
title_short | Neurotransmitter and Related Metabolic Profiling in the Nucleus Accumbens of Chronic Unpredictable Mild Stress-Induced Anhedonia-Like Rats |
title_sort | neurotransmitter and related metabolic profiling in the nucleus accumbens of chronic unpredictable mild stress induced anhedonia like rats |
topic | major depressive disorder chronic unpredictable mild stress nucleus accumbens neurotransmitter 5-HT glutamate |
url | https://www.frontiersin.org/articles/10.3389/fnbeh.2022.862683/full |
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