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Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice

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机构: [1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea [2]Department of Biochemistry, ChungnamNational University School of Medicine, Daejeon, South Korea [3]Infection Control Convergence Research Center, Chungnam National University School ofMedicine, Daejeon, South Korea [4]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea [5]Department ofAnesthesiology, The First People’s Hospital of Yunnan Province [T]he Affiliated Hospital of Kunming University of Science and Technology, Kunming, China [6]Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, South Korea [7]Department of Anesthesiology and PainMedicine, Chungnam National University School of Medicine, Daejeon, South Korea [8]Division of National Supercomputing, Korea Institute of Science andTechnology Information (KISTI), Daejeon, South Korea [9]Department of Neuroscience, College of Medicine, Korea University, Seoul, South Korea [10]CellModel Research Group, Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, South Korea
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Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg(-1), 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg(-1)) and nicotine (0.5 mg kg(-1)). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life. Juvenile mice treated with ketamine at anesthetic doses develop sex-specific differences in conditioned place-preference behavior and neuronal excitability, suggesting that repeated ketamine exposure might influence drug reward behavior later in life.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 1 区 生物学
最新[2023]版:
大类 | 1 区 生物学
小类 | 1 区 生物学
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出版当年[2021]版:
Q1 BIOLOGY
最新[2023]版:
Q1 BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea [2]Department of Biochemistry, ChungnamNational University School of Medicine, Daejeon, South Korea [3]Infection Control Convergence Research Center, Chungnam National University School ofMedicine, Daejeon, South Korea [4]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea [5]Department ofAnesthesiology, The First People’s Hospital of Yunnan Province
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通讯机构: [1]Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea [2]Department of Biochemistry, ChungnamNational University School of Medicine, Daejeon, South Korea [4]Brain Korea 21 FOUR Project for Medical Science, Chungnam National University, Daejeon, South Korea [6]Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, South Korea [7]Department of Anesthesiology and PainMedicine, Chungnam National University School of Medicine, Daejeon, South Korea
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