Dopaminergic Signaling in the Nucleus Accumbens Modulates Stress-Coping Strategies during Inescapable Stress
Journal of Neuroscience 40 巻 38 号
7241-7254 頁
2020-09-16 発行
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この文献の参照には次のURLをご利用ください : https://ir.lib.hiroshima-u.ac.jp/00051561
| ファイル情報(添付) | |
| タイトル ( eng ) |
Dopaminergic Signaling in the Nucleus Accumbens Modulates Stress-Coping Strategies during Inescapable Stress
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| 作成者 |
Aida Tomomi
Kobayashi Kenta
Wada Yusaku
Kato Shigeki
Zhu Meina
Isa Kaoru
Kobayashi Kazuto
Isa Tadashi
Tanaka Kohichi
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| 収録物名 |
Journal of Neuroscience
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| 巻 | 40 |
| 号 | 38 |
| 開始ページ | 7241 |
| 終了ページ | 7254 |
| 抄録 |
Maladaptation to stress is a critical risk factor in stress-related disorders, such as major depression and post-traumatic stress disorder (PTSD). Dopamine signaling in the nucleus accumbens (NAc) has been shown to modulate behavior by reinforcing learning and evading aversive stimuli, which are important for the survival of animals under environmental challenges such as stress. However, the mechanisms through which dopaminergic transmission responds to stressful events and subsequently regulates its downstream neuronal activity during stress remain unknown. To investigate how dopamine signaling modulates stress-coping behavior, we measured the subsecond fluctuation of extracellular dopamine concentration and pH using fast scanning cyclic voltammetry (FSCV) in the NAc, a postsynaptic target of midbrain dopaminergic neurons, in male mice engaged in a tail suspension test (TST). The results revealed a transient decrease in dopamine concentration and an increase in pH levels when the animals changed behaviors, from being immobile to struggling. Interestingly, optogenetic inhibition of dopamine release in NAc, potentiated the struggling behavior in animals under the TST. We then addressed the causal relationship of such a dopaminergic transmission with behavioral alterations by knocking out both the dopamine receptors, i.e., D1 and D2, in the NAc using viral vector-mediated genome editing. Behavioral analyses revealed that male D1 knock-out mice showed significantly more struggling bouts and longer struggling durations during the TST, while male D2 knock-out mice did not. Our results therefore indicate that D1 dopaminergic signaling in the NAc plays a pivotal role in the modulation of stress-coping behaviors in animals under tail suspension stress.
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| 著者キーワード |
animals
depression
dopamine
genome editing
striatum
voltammetry
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| 内容記述 |
This work was supported by the Program of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science, Natural Science Center for Basic Research and Development, Hiroshima University, and funds were provided by the Kato Memorial Bioscience Foundation. This work was also supported by Grants-in-Aid for Scientific Research on Innovative Areas (KAKENHI26112010 and JP19H05723), a Grant-in-Aid for Challenging Exploratory Research (KAKENHI17K19459) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), and a Grant-in-Aid for Integrated Research on Depression, Dementia and Development Disorders (20dm0107093h) carried out under the Strategic Research Program for Brain Sciences by Japan Agency for Medical Research and Development (AMED) (to H.A.).
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| 言語 |
英語
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| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Society for Neuroscience
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| 発行日 | 2020-09-16 |
| 権利情報 |
Copyright © 2020 the authors
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| 出版タイプ | Version of Record（出版社版。早期公開を含む） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 1529-2401
[ISSN] 0270-6474
[DOI] 10.1523/JNEUROSCI.0444-20.2020
[PMID] 32847967
[DOI] https://doi.org/10.1523/JNEUROSCI.0444-20.2020
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