Ketamine activated glutamatergic neurotransmission by GABAergic disinhibition in the medial prefrontal cortex
| Autor: | Lu-Yu Ye, Zhiqiang Liu, Yang Li, Xili Yang, Fan Guo, Jinqi Liu, Binglu Ye, Fei Guo, Zhendong Xu, Fuyi Shen, Qian Li, Rui Liu, Bing Zhang, Weijia Du |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Action Potentials Prefrontal Cortex Neurotransmission Receptors N-Methyl-D-Aspartate Synaptic Transmission 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic Mice 0302 clinical medicine Interneurons medicine Animals Ketamine GABAergic Neurons Prefrontal cortex Swimming Pharmacology business.industry musculoskeletal neural and ocular physiology Pyramidal Cells Psychotomimetic Antidepressive Agents Mice Inbred C57BL 030104 developmental biology nervous system Hindlimb Suspension Disinhibition NMDA receptor GABAergic medicine.symptom business Neuroscience Open Field Test 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology. 194 |
| ISSN: | 1873-7064 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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