Rapid Antidepressant Effect of Ketamine Correlates with Astroglial Plasticity in the Hippocampus

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BACKGROUND AND PURPOSE: Astroglia contributes to the pathophysiology of major depression and the action of antidepressant drugs through modulating synaptic plasticity; therefore, present study investigated whether fast antidepressant action of ketamine is reflected in the rapid alteration of the astrocytes morphology in a genetic animal model of depression.

EXPERIMENTAL APPROACH: S-Ketamine (15 mg/kg) or saline was administered as a single injection to Flinders Line (FSL/FRL) rats. Twenty-four hours after the treatment, perfusion fixation was carried out and the morphology of glial fibrillary acid protein (GFAP) positive astrocytes in the CA1 stratum radiatum area and the molecular layer of dentate gyrus of the hippocampus was investigated applying stereological techniques and by analyzing with Imaris software. Moreover, the depressive-like behavior of animals was evaluated using forced swim test.

KEY RESULTS: In the present study, FSL rats with ketamine treatment exhibited a significant reduction in the immobility time in comparison with FSL-vehicle group. Regarding the volume changes of hippocampus, we observed a significant increase in the volume of CA1.SR and GCL areas one day after ketamine treatment in FSL-rats, and that FSL rats following ketamine treatment showed considerably larger size of astrocytes in comparison with the FSL-vehicle group. Additionally, the number and the length of the astrocytic processes in the CA1.SR area was significantly increased one day following ketamine treatment.

CONCLUSION: Our results support the hypothesis that astrocytes atrophy contributes in the pathophysiology of depression and the morphological modification of astrocytes could be one of the mechanisms by which ketamine improves depressive behavior quickly.

Original languageEnglish
JournalBritish Journal of Pharmacology
Volume174
Issue6
ISSN0007-1188
DOIs
Publication statusPublished - 2017

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