Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model
Background: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antago...
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doaj-e68669a9869f4641940a808a8d1286832020-11-25T03:05:55ZengElsevierComprehensive Psychiatry0010-440X2020-10-01102152200Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression modelZhinan Li0Guodong Wang1Shuming Zhong2Xiaoxiao Liao3Shunkai Lai4Yanyan Shan5Junhao Chen6Lu Zhang7Qianyi Lu8Shiyi Shen9Hui Huang10Yiliang Zhang11Li Zhang12Yanbin Jia13Psychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, China; Psychiatry Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Transplantation Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaPsychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaPsychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaPsychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaJinan University, Guangzhou, ChinaPsychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaGHM Institute of CNS Regeneration, Jinan University, Guangzhou, China; Correspondence to: L. Zhang, GHM Institute of CNS Regeneration, Jinan University, 601 West Huangpu Avenue, Guangzhou 510632, China.Psychiatry Department, The First Affiliated Hospital of Jinan University, Guangzhou, China; Correspondence to: Y. Jia, Psychiatry Department, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou 510630, China.Background: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antagonist memantine on cognitive deficits in depression and the underlying mechanisms. Methods: Adult male Sprague-Dawley rats received corticosterone (CORT) (20 mg/kg) bi-weekly via subcutaneous injection and/or copper gluconate (7 mg/kg) via daily intragastric administration. After 3 weeks, sucrose preference tests and open field tests showed anhedonia and high anxiety in both the CORT and CORT+Cu groups. Memantine intervention (20 mg/kg daily via intragastric administration for 14 days) led to recovery of anhedonia and anxiety behaviors. Memantine also remarkably suppressed serum copper ion levels. Moreover, memantine treatment effectively rescued depression-related spatial memory deficits as shown by the Morris water maze task. Results: Compared to the pre-memantine treatment results, the results of behavioral tests and cognitive function after memantine treatment were significantly normalized, and the copper concentration was decreased in all groups. Conclusions: Collectively, our findings suggest that the NMDA receptor antagonist memantine may improve symptoms of anhedonia and anxiety and the cognitive deficits associated with depression, likely be related to suppress serum copper ion levels.http://www.sciencedirect.com/science/article/pii/S0010440X20300420DepressionNMDA receptorCopper ionsMemantineCognitive function |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhinan Li Guodong Wang Shuming Zhong Xiaoxiao Liao Shunkai Lai Yanyan Shan Junhao Chen Lu Zhang Qianyi Lu Shiyi Shen Hui Huang Yiliang Zhang Li Zhang Yanbin Jia |
spellingShingle |
Zhinan Li Guodong Wang Shuming Zhong Xiaoxiao Liao Shunkai Lai Yanyan Shan Junhao Chen Lu Zhang Qianyi Lu Shiyi Shen Hui Huang Yiliang Zhang Li Zhang Yanbin Jia Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model Comprehensive Psychiatry Depression NMDA receptor Copper ions Memantine Cognitive function |
author_facet |
Zhinan Li Guodong Wang Shuming Zhong Xiaoxiao Liao Shunkai Lai Yanyan Shan Junhao Chen Lu Zhang Qianyi Lu Shiyi Shen Hui Huang Yiliang Zhang Li Zhang Yanbin Jia |
author_sort |
Zhinan Li |
title |
Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model |
title_short |
Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model |
title_full |
Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model |
title_fullStr |
Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model |
title_full_unstemmed |
Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model |
title_sort |
alleviation of cognitive deficits and high copper levels by an nmda receptor antagonist in a rat depression model |
publisher |
Elsevier |
series |
Comprehensive Psychiatry |
issn |
0010-440X |
publishDate |
2020-10-01 |
description |
Background: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antagonist memantine on cognitive deficits in depression and the underlying mechanisms. Methods: Adult male Sprague-Dawley rats received corticosterone (CORT) (20 mg/kg) bi-weekly via subcutaneous injection and/or copper gluconate (7 mg/kg) via daily intragastric administration. After 3 weeks, sucrose preference tests and open field tests showed anhedonia and high anxiety in both the CORT and CORT+Cu groups. Memantine intervention (20 mg/kg daily via intragastric administration for 14 days) led to recovery of anhedonia and anxiety behaviors. Memantine also remarkably suppressed serum copper ion levels. Moreover, memantine treatment effectively rescued depression-related spatial memory deficits as shown by the Morris water maze task. Results: Compared to the pre-memantine treatment results, the results of behavioral tests and cognitive function after memantine treatment were significantly normalized, and the copper concentration was decreased in all groups. Conclusions: Collectively, our findings suggest that the NMDA receptor antagonist memantine may improve symptoms of anhedonia and anxiety and the cognitive deficits associated with depression, likely be related to suppress serum copper ion levels. |
topic |
Depression NMDA receptor Copper ions Memantine Cognitive function |
url |
http://www.sciencedirect.com/science/article/pii/S0010440X20300420 |
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