氯胺酮诱导小鼠脑网络激活研究  

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

作　　者：钟嘉峰 胥亮 周锐奕 陈波 朱英杰 李蕾 徐薇 ZHONG Jiafeng;XU Liang;ZHOU Ruiyi;CHEN Bo;ZHU Yingjie;LI Lei;XU Wei(Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;Shenzhen University of Advanced Technology,Shenzhen 518000,China;University of Chinese Academy of Sciences,Beijing 100049,China;Shenzhen Key Laboratory of Drug Addiction,Shenzhen 518055,China;West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[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]四川大学华西公共卫生学院,成都610041

出　　处：《集成技术》2025年第2期109-124,共16页Journal of Integration Technology

基　　金：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)。

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。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.

关 键 词：氯胺酮 脑网络 cFos蛋白 

分 类 号：Q189[生物学—神经生物学]