Intravascular Ketamine Increases Theta-Burst but Not High Frequency Tetanus Induced LTP at CA3-CA1 Synapses Within Three Hours and Devoid of an Increase in Spine Density.
Allie J Widman, Amy E Stewart, Elise M Erb, Elizabeth A Gardner, Lori L McMahon
Frontiers in Synaptic Neuroscience 2018 DOI: 10.3389/fnsyn.2018.00008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats (in vivo ketamine administration; hippocampal slices) |
| Intervention | Ketamine |
| Duration | 3 hours post ketamine administration |
| Measures | theta-burst induced long-term potentiation (LTP), high frequency tetanus induced LTP, basal synaptic function, spine density |
| Topics | Ketamine Neuroplasticity Esketamine |
| Keywords | Anti-depressants Hippocampus Spine density |
| Key findings | Theta-burst-induced long-term potentiation at CA3-CA1 synapses was significantly increased 3 hours after in vivo intravenous ketamine, whereas high-frequency tetanus-induced LTP was not. Basal synaptic function and spine density were unchanged. The authors argue this supports increased activity-dependent hippocampal function as a mechanism for ketamine's rapid antidepressant effects. |
Abstract
In the past 20 years, ketamine has become a promising treatment for Major Depressive Disorder (MDD) due to its rapid and sustain antidepressant effects in patients. A single ketamine treatment causes improvement in depressive symptoms within hours and can last weeks, long after it is eliminated. Previous studies have demonstrated increased synaptic plasticity at CA3-CA1 synapses in hippocampus (HPC) 24 h post ketamine treatment suggesting increased activity-dependent hippocampal function may underlie the antidepressant effects of ketamine. If true, these changes should also occur within hours of treatment, a time when symptoms are first alleviated in patients. To determine if augmented synaptic plasticity is observed at an earlier time point, we measured theta-burst and high frequency tetanus induced long-term potentiation (LTP) at CA3-CA1 synapses 3 h following intravenous (IV) ketamine administration. Additionally, we measured basal hippocampal function and spine density to investigate whether connectivity was increased with ketamine treatment. We report that theta-burst but not high frequency tetanus induced LTP is significantly increased 3 h after in vivo ketamine with no changes in basal synaptic function or morphology. Our finding supports increased activity-dependent hippocampal function underlying the antidepressant effects of ketamine as it occurs at a time point that correlates with initial improvements of depressive symptoms in patients.
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
Cited by 13
- NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine Journal of Neuroscience January 3, 2023
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions. Molecular Psychiatry April 1, 2024
- Ketamine induced synaptic plasticity operates independently of long-term potentiation. Neuropsychopharmacology October 1, 2024
- Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity. Neuropsychopharmacology May 1, 2025
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine. Molecular Psychiatry July 7, 2025
and 8 more in the library
Cites 12
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- NEUROBIOLOGY OF STRESS, DEPRESSION, AND RAPID ACTING ANTIDEPRESSANTS: REMODELING SYNAPTIC CONNECTIONS Depression and Anxiety March 10, 2014
and 7 more in the library