氯胺酮诱导小鼠脑网络激活研究
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Q 189

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国家科技创新 2030 重大项目(2021ZD0202103);广东省科技厅项目(2023B1515040009, 2023A1515012122);深圳市科技创新委员会项目(KCXFZ20230731100901004, KCXFZ20211020164543007);深圳市医学科研基金项目(SMRFA2303034)


Research on the Activation of Brain Networks Induced by Ketamine in Mice
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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-天冬氨酸受体拮抗剂,临床上用于镇静、麻醉和治疗难治性抑郁症,但是氯胺酮的成瘾性限制了其临床应用。0.5 mg/kg 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。目前,不同剂量的氯胺酮对脑网络的激活情况仍不清楚。本文选择 0.5 mg/kg 和 15 mg/kg 两个有代表性的氯胺酮剂量,腹腔连续注射 7 d,通过检测脑即刻早期基因蛋白(cFos)的表达评估氯胺酮对小鼠脑网络的激活情况。结果表明,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 阳性细胞数量;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 阳性细胞数量。由此表明: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了基础,为寻找氯胺酮抗抑郁和成瘾差异脑区提供了参考。

    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 broader 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 associated with abuse. 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). The 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 provides a foundation for investigating the neuropharmacological effects of different ketamine doses and investigating brain regions associated with its antidepressant and addictive properties.

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引文格式
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,2025,14(2):109-124

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,2025,14(2):109-124

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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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