氯胺酮诱导小鼠脑网络激活研究
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1(中国科学院深圳先进技术研究院,深圳 518055)3(中国科学院大学,北京 100049);2.4(深圳市药物成瘾重点实验室,深圳 518055)6(四川大学华西公共卫生学院,成都 610041);3.4(深圳市药物成瘾重点实验室,深圳 518055);4.1(中国科学院深圳先进技术研究院,深圳 518055)3(中国科学院大学,北京 100049) 4(深圳市药物成瘾重点实验室,深圳 518055) 5(深圳毒品联合实验室,深圳 518055);5.1(中国科学院深圳先进技术研究院,深圳 518055) 2(深圳理工大学,深圳 518000) 3(中国科学院大学,北京 100049) 4(深圳市药物成瘾重点实验室,深圳 518055) 5(深圳毒品联合实验室,深圳 518055)

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中国科技创新2030重大项目(2021ZD0202103);广东省科技厅(2023B1515040009 & 2023A1515012122);深圳市科技创新委员会(KCXFZ20230731100901004 & KCXFZ20211020164543007);深圳市医学科研基金(SMRFA2303034)

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Research on the Activation of Brain Networks Induced by Ketamine in Mice
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Affiliation:

1 (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China)3(University of Chinese Academy of Sciences, Beijing 100049, China);2.4(Shenzhen Key Laboratory of Drug Addiction, Shenzhen 518055, China)6(West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.);3.4(Shenzhen Key Laboratory of Drug Addiction, Shenzhen 518055, China);4.1 (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China)3(University of Chinese Academy of Sciences, Beijing 100049, China) 4(Shenzhen Key Laboratory of Drug Addiction, Shenzhen 518055, China)5(Shenzhen Joint Drug Laboratory, Shenzhen 518055, China);5.1 (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China) 2(Shenzhen University of Advanced Technology, Shenzhen 518055, China) 3(University of Chinese Academy of Sciences, Beijing 100049, China) 4(Shenzhen Key Laboratory of Drug Addiction, Shenzhen 518055, China) 5(Shenzhen Joint Drug Laboratory, Shenzhen 518055, China)

Funding:

the Major Project of the Science and Technology Innovation 2030 of China (2021ZD0202103), Department of Science and Technology of Guangdong Province (2023B1515040009 & 2023A1515012122), Technology and Innovation Commission of Shenzhen (KCXFZ20230731100901004 & KCXFZ20211020164543007), Shenzhen Medical Research Fund(SMRFA2303034)

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    摘要:

    氯胺酮是一种N-甲基-d-天冬氨酸受体(NMDARs)拮抗剂,在临床上被用于镇静、麻醉以及治疗难治性抑郁,但是氯胺酮的成瘾性限制了其临床应用。0.5 mg/kg 剂量是临床常用的氯胺酮抗抑郁剂量,而15 mg/kg是氯胺酮滥用人群的暴露剂量[1]。目前有关不同剂量氯胺酮对脑网络的激活情况仍不清楚。本实验选择0.5 mg/kg 及15 mg/kg 两个有代表性的氯胺酮剂量,腹腔连续注射7天,通过脑即刻早期基因蛋白(cFos)表达量来表征氯胺酮对小鼠脑网络的激活情况。结果显示,与生理盐水组相比,0.5 mg/kg 氯胺酮能显著增加内侧前额叶、中间外侧隔核、导水管周围灰质脑区 cFos 数量;而15 mg/kg 氯胺酮能显著增加伏隔核、外侧缰核、 海马CA3、杏仁核、腹侧被盖区 cFos 表达数量。这说明氯胺酮对脑网络的激活呈剂量依赖性,0.5 mg/kg和15 mg/kg的氯胺酮激活的脑区存在差异。该研究为探索不同剂量氯胺酮的神经药理作用奠定基础,为寻找氯胺酮抗抑郁和成瘾差异脑区提供参考。

    Abstract:

    Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, is clinically utilized for sedation, anesthesia, and the treatment of refractory depression. However, its addictive properties restrict its clinical application. A dose of 0.5 mg/kg is commonly used as an antidepressant in clinical settings, while 15 mg/kg represents the dose typically abused. The effects of varying doses of ketamine on brain network activation remain unclear. In this experiment, two representative doses of ketamine, 0.5 mg/kg and 15 mg/kg, were administered via intraperitoneal injection for 7 consecutive days. Brain network activation was assessed by examining the expression of the immediate early gene protein (cFos). Results indicated that, compared to the saline control group, 0.5 mg/kg ketamine significantly increased the number of cFos-positive cells in the medial prefrontal cortex, intermediate lateral septal nucleus, and periaqueductal gray matter. Conversely, 15 mg/kg ketamine significantly increased cFos expression in the nucleus accumbens, lateral habenula, hippocampal CA3 region, amygdala, and ventral tegmental area. These findings suggest that ketamine"s activation of brain networks is dose-dependent, with different doses activating distinct brain regions. This study lays a foundation for investigating the neuropharmacological effects of different ketamine doses and provides a reference for identifying brain regions associated with its antidepressant and addictive properties.

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钟嘉峰,胥亮,周锐奕,等.氯胺酮诱导小鼠脑网络激活研究 [J].集成技术,

Citing format
Zhong Jiafeng, Xu Liang, Zhou Ruiyi, et al. Research on the Activation of Brain Networks Induced by Ketamine in Mice[J]. Journal of Integration Technology.

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  • 收稿日期:2024-08-09
  • 最后修改日期:2024-09-11
  • 录用日期:2024-09-12
  • 在线发布日期: 2024-09-30
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