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Locus Coeruleus-Noradrenergic Neurons Regulate Stress Coping During Subchronic Exposure to Social Threats: A Characteristic Feature in Postpartum Female Mice


Stress-coping strategies have been implicated in depression. The control of stress coping may improve the symptom and higher prevalence of depression during the postpartum period in women. However, the neuronal mechanisms underlying stress coping remain to be fully elucidated in postpartum women. In this study, we examined how locus coeruleus-noradrenergic (LC-NA) neurons, which have been associated with both stress coping and depression, regulate changes in coping style induced by subchronic exposure to unfamiliar male mice as a social threat in postpartum female mice. In contrast to virgin females, dams exposed to unfamiliar males daily for four consecutive days showed reduced immobility duration in the forced swim test, indicating that exposure to unfamiliar males decreased passive stress coping in dams. Exposure to unfamiliar males also decreased sucrose palatability in the sucrose preference test and suppressed the crouching behavior in the maternal care test but did not affect anxiety-like behavior in the hole-board test in dams. In fiber photometry analyses, LC-NA neurons showed differential activity between dams and virgin females in response to unfamiliar males. Chemogenetic inhibition of LC-NA neurons during exposure to unfamiliar males prevented the social threat-induced decrease in immobility duration in the forced swim test in dams. Furthermore, inhibition or activation of LC-NA neurons exacerbated crouching behavior in dams. These results indicate that LC-NA neurons regulate the social threat-induced decrease in passive stress coping and relieve social threat-induced inhibition of maternal care in postpartum female mice.

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Data supporting the main findings and conclusions of this study are included in the article. All datasets and analyses used in this study are available from the corresponding author upon request.


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We thank Dr. Kazuto Kobayashi (Fukushima Medical University) for providing DBH-Cre/6-8 mice. We thank Dr. Bryan Roth (UNC Eshelman School of Pharmacy) for providing AAVs.


This work was supported by JSPS KAKENHI [Grant No: 17K08119, 18H04601], the Akiyama Life Science Foundation [Grant No: 111–076], and the Takeda Science Foundation.

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All authors contributed to the conception and design of the study. AN and YM contributed to the acquisition, analysis, and interpretation of data. YM drafted the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Yoshikage Muroi.

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The authors have no relevant financial or non-financial interests to disclose.

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All procedures in this study were performed following the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80–23; revised 2011) and approved by the Animal Research Committee of the Obihiro University of Agriculture and Veterinary Medicine.

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Nakamura, A., Muroi, Y. & Ishii, T. Locus Coeruleus-Noradrenergic Neurons Regulate Stress Coping During Subchronic Exposure to Social Threats: A Characteristic Feature in Postpartum Female Mice. Cell Mol Neurobiol 43, 2359–2376 (2023).

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