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Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm

Authors
 Jeho Seo  ;  Hojin Cho  ;  Gun Tae Kim  ;  Chul Hoon Kim  ;  Dong Goo Kim 
Citation
 Neuroimage, Vol.159 : 207-213, 2017 
Journal Title
 Neuroimage 
ISSN
 1053-8119 
Issue Date
2017
MeSH
Adaptation, Psychological/physiology ; Animals ; Dentate Gyrus/metabolism ; Dentate Gyrus/physiopathology ; Depressive Disorder, Major/metabolism ; Depressive Disorder, Major/physiopathology ; Glutamine/metabolism ; Helplessness, Learned ; Rats ; Stress, Psychological/physiopathology
Keywords
Coping strategy ; Learned helplessness ; Major depressive disorder ; Resting brain activity ; Stress
Abstract
BACKGROUND: Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). METHODS: We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. RESULTS: After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. CONCLUSION: Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161196
Full Text
https://www.sciencedirect.com/science/article/pii/S1053811916307698
DOI
10.1016/j.neuroimage.2016.12.047
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실)
Yonsei Authors
김동구(Kim, Dong Goo)
김철훈(Kim, Chul Hoon)
조호진(Cho, Hojin)
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