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(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats

文献类型：期刊论文

作者Liu, Lifen7; Li, Rui7; Wu, Lanxia7; Guan, Yubo6; Miao, Miao6; Wang, Yuxuan6; Li, Changjiang7; Wu, Chunyan2; Lu, Guohua7; Hu, Xinyu1,5,7
刊名PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
出版日期2024-12-01
卷号245页码:16
关键词Post-traumatic stress disorder Negative emotions PI3K/AKT signaling pathway (2R 6R)-HNK
ISSN号0091-3057
DOI10.1016/j.pbb.2024.173891
通讯作者Hu, Xinyu(huxy@psych.ac.cn) ; Sun, Lin(linsun2013@sdsmu.edu.cn)
英文摘要Background: Patients diagnosed with post-traumatic stress disorder (PTSD) mainly exhibit enduring adverse emotions, heightening susceptibility to suicidal thoughts and behaviors. Notably, metabolites of ketamine, particularly (2R,6R)-hydroxyketamine (HNK), have demonstrated favorable antidepressant properties. However, the precise mechanism through which HNK exerts its therapeutic effects on negative emotional symptoms in PTSD patients should be fully elucidated. Methods: In this investigation, a model involving a single prolonged stress and plantar shock (SPS&S) was utilized, followed by the administration of (2R, 6R)-HNK into the lateral ventricle subsequent to the recovery phase. The evaluation of PTSD-related behaviors was conducted through the open field test (OFT), elevated plus maze test (EMPT), and forced swim test (FST). The expression of phosphatidylinositol 3-kinase (PI3K)/phosphokinase B (AKT) signaling pathway in rat brain regions was analyzed using molecular biology experiments. Results: SPS&S rats displayed adverse emotional behaviors characterized by depression and anxiety. Treatment with (2R, 6R)-HNK enhanced exploratory behavior and reversed negative emotional behaviors. This intervention mitigated disruptions in the expression levels of PI3K/AKT signaling pathway-associated proteins in the HIP and PFC, without influencing PI3K/AKT signaling in the AMY of SPS&S rats. Conclusion: Traumatic stress can trigger negative emotional reactions in rats, potentially involving the PI3K/AKT signaling pathway in the HIP, PFC, and AMY. The (2R, 6R)-HNK compounds have demonstrated the potential to mitigate adverse emotions in rats subjected to the SPS&S paradigm. This effect may be attributed to the modulation of the PI3K/AKT signaling pathway in the HIP, and PFC, with a particularly notable impact observed in the HIP region.
收录类别SCI
WOS关键词POSTTRAUMATIC-STRESS-DISORDER ; SINGLE-PROLONGED STRESS ; KETAMINE ; HIPPOCAMPUS ; MODEL ; MECHANISMS ; EXPRESSION ; PLASTICITY ; GLUTAMATE ; NEURONS
资助项目Institute of Psychology, Chinese Academy of Sciences[GJ202002] ; National Natural Science Foundation of China (NSFC)[82101588] ; Surface project of Natural Science Foundation of Shandong Province[ZR2020MC218]
WOS研究方向Behavioral Sciences ; Neurosciences & Neurology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001333161900001
出版者PERGAMON-ELSEVIER SCIENCE LTD
资助机构Institute of Psychology, Chinese Academy of Sciences ; National Natural Science Foundation of China (NSFC) ; Surface project of Natural Science Foundation of Shandong Province
源URL[http://ir.psych.ac.cn/handle/311026/49114]  
专题心理研究所_中国科学院心理健康重点实验室
通讯作者Hu, Xinyu; Sun, Lin
作者单位1.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
2.Shandong Second Med Univ, Affiliated Hosp, Dept Neurol, Weifang, Peoples R China
3.Management Comm Shanting Econ Dev Zone, 37 Fuqian Rd, Zaozhuang 277200, Shandong, Peoples R China
4.Shanting Dist Peoples Hosp, Dept Neurosurg, Beijing Rd, Zaozhuang 277200, Shandong, Peoples R China
5.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
6.Shandong Second Med Univ, Sch Clin Med, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China
7.Shandong Second Med Univ, Sch Psychol, 7166 Baotong West St, Weifang 261053, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Lifen,Li, Rui,Wu, Lanxia,et al. (2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,2024,245:16.
APA Liu, Lifen.,Li, Rui.,Wu, Lanxia.,Guan, Yubo.,Miao, Miao.,...&Sun, Lin.(2024).(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats.PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR,245,16.
MLA Liu, Lifen,et al."(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats".PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 245(2024):16.

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来源：心理研究所

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