Orexinergic neurons modulate stress coping responses in mice

Jae Gon Kim, Ji Yun Ea, Bong June Yoon

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Stress is a critical precipitating factor for major depression. However, individual responses to the same stressor vary widely, possibly owing to individual variations in stress resilience. Nevertheless, the factors that determine stress susceptibility and resilience remain poorly understood. Orexin neurons have been implicated in the control of stress-induced arousal. Therefore, we investigated whether orexin-expressing neurons are involved in the regulation of stress resilience in male mice. We found that the level of c-fos expression was significantly different in susceptible versus resilient mice in the learned helplessness test (LHT). Furthermore, activating orexinergic neurons induced resilience in the susceptible group, and this resilience was also consistently observed in other behavioral tests. However, activating orexinergic neurons during the induction period (during inescapable stress exposure) did not affect stress resilience in the escape test. In addition, analyses using pathway-specific optic stimulation revealed that activating orexinergic projections to the medial part of the nucleus accumbens (NAc) alone mediated a decrease in anxiety but was not sufficient to induce resilience in the LHT. Collectively, our data suggest that orexinergic projections to multiple targets control diverse and flexible stress-related behaviors in response to various stressors.

Original languageEnglish
Article number1140672
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 2023

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning of the Republic of Korea (nos. NRF-2014R1A2A1A11053247 and NRF-2021R1I1A2052948) and a Korea University research grant.

Publisher Copyright:
Copyright © 2023 Kim, Ea and Yoon.


  • anxiety
  • chemogenetics
  • major depressive disorder
  • optogenetics
  • orexin
  • resilience
  • stress coping

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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