Neurovascular plasticity of the hippocampus one week after a single dose of ketamine in genetic rat model of depression.
Maryam Ardalan, Gregers Wegener, Benedetta Polsinelli, Torsten M Madsen, Jens R Nyengaard
Hippocampus November 2016 DOI: 10.1002/hipo.22617 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats |
| Intervention | Ketamine |
| Dose | 15 mg/kg |
| Duration | Single injection, tissue examined 7 days later |
| Measures | optical fractionator method, global spatial sampling method, physical disector method |
| Topics | Depression Neuroplasticity Esketamine Ketamine |
| Keywords | Antidepressant Flinders line Stereology |
| Key points | A single ketamine injection (15 mg/kg) given 7 days before tissue analysis was associated with larger hippocampal volume, more non-perforated synapses, more dentate gyrus neurons, and greater microvessel length in FSL rats compared with saline-treated FSL rats. The authors propose these neurovascular changes may contribute to ketamine's sustained antidepressant effect. |
Abstract
Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus. © 2016 Wiley Periodicals, Inc.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 3
- Shared effects of electroconvulsive shocks and ketamine on neuroplasticity: A systematic review of animal models of depression. Neuroscience & Biobehavioral Reviews September 1, 2024
- Research Progress on the Mechanism of Ketamine in Neuropathic Pain Comorbid Depression Neuropsychiatric Disease and Treatment August 9, 2025
- Ventral CA3 Activation Mediates Prophylactic Ketamine Efficacy Against Stress-Induced Depressive-Like Behavior Biological Psychiatry February 23, 2018
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