Astrocytes activation contributes to the antidepressant-like effect of ketamine but not scopolamine.
Yun Wang, Liming Xie, Ce Gao, Lingyan Zhai, Ning Zhang, Lin Guo
Pharmacology, Biochemistry, and Behavior July 2018 DOI: 10.1016/j.pbb.2018.05.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rodents (rats or mice) used in behavioral and biochemical experiments |
| Interventions | Ketamine Scopolamine Fluorocitrate |
| Measures | GFAP expression, forced swim test (FST), tail suspension test (TST) |
| Topics | Ketamine Esketamine |
| Keywords | Antidepressants Astrocyte Scopolamine |
| Key points | Ketamine, but not scopolamine, significantly increased hippocampal GFAP expression, and inhibiting astrocytes with fluorocitrate abolished ketamine's antidepressant-like effects in the forced swim and tail suspension tests but not scopolamine's. The authors suggest activated astrocytes play a vital role in ketamine's antidepressant activity rather than scopolamine's. |
Abstract
Depression is a common, debilitating mood disorder, but currently available antidepressants have several major drawbacks. Both ketamine and scopolamine attract more and more attention due to their rapid and sustained antidepressant activities. However, the molecular and cellular mechanism that underlies the therapeutic action of ketamine and scopolamine still remain to be elucidated. Considering the importance of astrocytes in the development of depression, we hypothesized that the activation of astrocyte may play a vital role in the antidepressant effects of ketamine and scopolamine. In the present study, the expression of fibrillary acidic protein (GFAP) was detected to evaluate the activation of astrocyte after single injection of ketamine and scopolamine in respective efficient doses. Behavioral tests used to assess antidepressant-like effects were forced swim test (FST) and tail suspension test (TST). Fluorocitrate, a well-established astrocyte inactivator, was adopted to inhibit the activation of astrocyte. The results demonstrated that ketamine, but not scopolamine, could increase significantly the expression of GFAP in hippocampus. In addition, inhibition of astrocyte abolished the antidepressant-like effects of ketamine, but not scopolamine in the FST and TST. It is suggested that activated astrocyte plays a vital role in the antidepressant activities of ketamine rather than scopolamine. These findings may be important for the understanding of the role of astrocyte in depression and antidepressants, especially rapid antidepressants.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
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- Effects of stress on endophenotypes of suicide across species: A role for ketamine in risk mitigation Neurobiology of Stress April 20, 2022
- Ketamine and fluoxetine exert similar actions on prelimbic and infralimbic responsivity to lateral septal nucleus stimulation in Wistar rats. Neuroscience Letters June 21, 2024
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Cites 6
- Role of 5-HT1A Receptor Stimulation in the Medial Prefrontal Cortex in the Sustained Antidepressant Effects of Ketamine The International Journal of Neuropsychopharmacology December 22, 2017
- Novel rapid-acting antidepressants: molecular and cellular signaling mechanisms. Neuronal signaling December 2017
- Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants Frontiers in Pharmacology October 14, 2013
- Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology Molecular Psychiatry January 3, 2012
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
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