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ID 51561
file
creator
Aida, Tomomi
Kobayashi, Kenta
Wada, Yusaku
Kato, Shigeki
Zhu, Meina
Isa, Kaoru
Kobayashi, Kazuto
Isa, Tadashi
Tanaka, Kohichi
subject
animals
depression
dopamine
genome editing
striatum
voltammetry
abstract
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.
description
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.).
journal title
Journal of Neuroscience
volume
Volume 40
issue
Issue 38
start page
7241
end page
7254
date of issued
2020-09-16
publisher
Society for Neuroscience
issn
1529-2401
0270-6474
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
publisher
rights
Copyright © 2020 the authors
relation url
department
Graduate School of Biomedical & Health Sciences