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

Jianchen Cui, Xianshu Ju, Yulim Lee, Boohwi Hong, Hyojin Kang, Kihoon Han, Won Ho Shin, Jiho Park, Min Joung Lee, Yoon Hee Kim, Youngkwon Ko, Jun Young Heo, Woosuk Chung

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number709
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF), Grant number: NRF- 2017R1A5A2015385, NRF-2018R1C1B6003139, NRF-2019M3E5D1A02068575.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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