Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress
Social stress, a common stressor, causes multiple forms of physical and mental dysfunction. Prolonged exposure to social stress is associated with a higher risk of psychological disorders, including anxiety disorders and major depressive disorder (MDD). The orexinergic system is involved in the regu...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-05-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289521000060 |
| _version_ | 1818945136412852224 |
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| author | Dan Wang Ao Li Keyi Dong Huihui Li Yongxin Guo Xinxin Zhang Min Cai Huiming Li Guangchao Zhao Qianzi Yang |
| author_facet | Dan Wang Ao Li Keyi Dong Huihui Li Yongxin Guo Xinxin Zhang Min Cai Huiming Li Guangchao Zhao Qianzi Yang |
| author_sort | Dan Wang |
| collection | DOAJ |
| description | Social stress, a common stressor, causes multiple forms of physical and mental dysfunction. Prolonged exposure to social stress is associated with a higher risk of psychological disorders, including anxiety disorders and major depressive disorder (MDD). The orexinergic system is involved in the regulation of multiple motivated behaviors. The current study examined the regulatory effect of orexinergic projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) in depression- and anxiety-like behaviors after chronic social defeat stress. When mice were defeated during social interaction, both orexinergic neurons in the LHA and glutamatergic neurons in the LHb were strongly activated, as indicated by the FosTRAP strategy. Infusion of orexin in the LHb significantly alleviated social avoidance and depression-like behaviors induced by chronic social defeat stress. Administration of an orexin receptor 2 antagonist in the LHb further aggravated the depressive phenotype. Photoactivation of orexinergic cell bodies in the LHA or terminals in the LHb relieved anxiety-like behaviors induced by chronic social defeat stress. Collectively, we identified the antidepressant and anxiolytic effects of the circuit from LHA orexinergic neurons to the LHb in response to chronic social stress, providing new evidence of the antidepressant properties of LHA orexin circuits. |
| first_indexed | 2024-12-20T07:54:19Z |
| format | Article |
| id | doaj.art-062a6d16543e430eb327f2a3aa8ab40e |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-12-20T07:54:19Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-062a6d16543e430eb327f2a3aa8ab40e2022-12-21T19:47:44ZengElsevierNeurobiology of Stress2352-28952021-05-0114100298Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stressDan Wang0Ao Li1Keyi Dong2Huihui Li3Yongxin Guo4Xinxin Zhang5Min Cai6Huiming Li7Guangchao Zhao8Qianzi Yang9Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Psychiatry, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, ChinaDepartment of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, China; Corresponding author.Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Xi'an, Shaanxi, China; Corresponding author. Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Changle Road, Xi'an, Shaanxi, 710032, China.Social stress, a common stressor, causes multiple forms of physical and mental dysfunction. Prolonged exposure to social stress is associated with a higher risk of psychological disorders, including anxiety disorders and major depressive disorder (MDD). The orexinergic system is involved in the regulation of multiple motivated behaviors. The current study examined the regulatory effect of orexinergic projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) in depression- and anxiety-like behaviors after chronic social defeat stress. When mice were defeated during social interaction, both orexinergic neurons in the LHA and glutamatergic neurons in the LHb were strongly activated, as indicated by the FosTRAP strategy. Infusion of orexin in the LHb significantly alleviated social avoidance and depression-like behaviors induced by chronic social defeat stress. Administration of an orexin receptor 2 antagonist in the LHb further aggravated the depressive phenotype. Photoactivation of orexinergic cell bodies in the LHA or terminals in the LHb relieved anxiety-like behaviors induced by chronic social defeat stress. Collectively, we identified the antidepressant and anxiolytic effects of the circuit from LHA orexinergic neurons to the LHb in response to chronic social stress, providing new evidence of the antidepressant properties of LHA orexin circuits.http://www.sciencedirect.com/science/article/pii/S2352289521000060Social defeat stressOrexinLateral hypothalamic areaLateral habenula |
| spellingShingle | Dan Wang Ao Li Keyi Dong Huihui Li Yongxin Guo Xinxin Zhang Min Cai Huiming Li Guangchao Zhao Qianzi Yang Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress Neurobiology of Stress Social defeat stress Orexin Lateral hypothalamic area Lateral habenula |
| title | Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| title_full | Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| title_fullStr | Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| title_full_unstemmed | Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| title_short | Lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| title_sort | lateral hypothalamus orexinergic inputs to lateral habenula modulate maladaptation after social defeat stress |
| topic | Social defeat stress Orexin Lateral hypothalamic area Lateral habenula |
| url | http://www.sciencedirect.com/science/article/pii/S2352289521000060 |
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