2. Academic Validation
  3. Ketamine activated glutamatergic neurotransmission by GABAergic disinhibition in the medial prefrontal cortex

Ketamine activated glutamatergic neurotransmission by GABAergic disinhibition in the medial prefrontal cortex

  • Neuropharmacology. 2021 Aug 15;194:108382. doi: 10.1016/j.neuropharm.2020.108382.
Bing Zhang 1,  Xili Yang 2,  Luyu Ye 3,  Rui Liu 2,  Binglu Ye 2,  Weijia Du 2,  Fuyi Shen 2,  Qian Li 2,  Fan Guo 3,  Jinqi Liu 4,  Fei Guo 3,  Yang Li 5,  Zhendong Xu 6,  Zhiqiang Liu 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China; Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.
  • 2 Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.
  • 3 Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai, 201203, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.
  • 4 The MacDuffie School, 66 School Street, Granby, MA, 01033, USA.
  • 5 Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai, 201203, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China. Electronic address: liyang@simm.ac.cn.
  • 6 Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China. Electronic address: btxzd123@51mch.com.
  • 7 Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China; Anesthesia and Brain Function Research Institute, Tongji University School of Medicine, Shanghai, 200082, China. Electronic address: liuzhiqiang@51mch.com.
PMID: 33144117 DOI: 10.1016/j.neuropharm.2020.108382
Abstract

The fast-onset antidepressant actions of ketamine at subanaesthetic doses have attracted enormous interest in psychiatric disease treatment. However, the severe psychotomimetic side effects foster an urgent need to deeply understand the fast-onset antidepressant mechanism of ketamine. Ketamine, as a non-competitive NMDAR antagonist, increases the overall excitability of the mPFC, which is presumed to be essential for the antidepressant action of ketamine. However, the underlying mechanism is still elusive. Here, our results showed that low concentration of ketamine increased the activity and the excitatory/inhibitory ratio of pyramidal neurons; these changes were accompanied by diminished interneurons activity in the mPFC. Moreover, ketamine induced increases in excitatory transmission and antidepressant-like effects, which might rely on the functional intact of GABAergic system in the mPFC. These results suggest a critical role of the mPFC GABAergic system in the fast antidepressant effects of a subanaesthetic dose ketamine.

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