Temporally dissociable effects of ketamine on neuronal discharge and gamma oscillations in rat thalamo-cortical networks.
Maria Amat-Foraster, Anders A. Jensen, Niels Plath, Kjartan F Herrik, Pau Celada, Francesc Artigas
Neuropharmacology July 15, 2018 DOI: 10.1016/j.neuropharm.2018.04.022 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Intervention | Ketamine |
| Dose | 0.25-5 mg/kg, i.v. |
| Topics | Ketamine Esketamine |
| Keywords | Local field potentials Nmda receptor antagonists Neuronal oscillations Single unit recordings Thalamo-cortical networks |
| Key findings | Ketamine (1, 2, and 5 mg/kg i.v.) decreased neuronal discharge in thalamo-cortical networks and increased gamma oscillations, with no disinhibition of excitatory neurons unlike phencyclidine. |
Abstract
Sub-anesthetic doses of the non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonist ketamine evoke transient psychotomimetic effects, followed by persistent antidepressant effects in treatment-resistant depressed patients and rodents through still poorly understood mechanisms. Since phencyclidine (PCP) disinhibits thalamo-cortical networks by blocking NMDA-Rs on GABAergic neurons of the reticular thalamic nucleus (RtN), we examined ketamine's actions in the same areas. Single units and local field potentials were recorded in chloral hydrate anesthetized male Wistar rats. The effects of cumulative ketamine doses (0.25-5 mg/kg, i.v.) on neuronal discharge and oscillatory activity were examined in RtN, mediodorsal and centromedial (MD/CM) thalamic nuclei, and layer VI of the medial prefrontal cortex (mPFC). Ketamine (1, 2 and 5 mg/kg, i.v.) significantly decreased the discharge of MD/CM, RtN and layer VI mPFC pyramidal neurons. Simultaneously, ketamine decreased the power of low frequency oscillations in all areas examined and increased gamma oscillations in mPFC and MD/CM. Lower ketamine doses (0.25 and 0.5 mg/kg, i.v.) were ineffective. As observed for PCP, ketamine markedly inhibited the activity of RtN neurons. However, unlike PCP, this effect did not translate into a disinhibition of MD/CM and mPFC excitatory neurons, possibly due to a more potent and simultaneous blockade of NMDA-Rs by ketamine in MD/CM and mPFC neurons. Hence, the present in vivo results show that ketamine evokes an early transient inhibition of neuronal discharge in thalamo-cortical networks, following its rapid pharmacokinetics, which is likely associated to its psychotomimetic effects. The prolonged increase in gamma oscillations may underlie its antidepressant action.
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 11
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Effect of Low-Dose Esketamine on Postoperative Delirium in Elderly Patients Undergoing Total Hip or Knee Arthroplasty: A Randomized Controlled Trial. Drug Design, Development and Therapy 2024
- Computational modeling of ketamine-induced changes in gamma-band oscillations: The contribution of parvalbumin and somatostatin interneurons. PLoS Computational Biology June 9, 2025
and 6 more in the library
Cites 25
- 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
- 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 Journal of Neuroscience April 15, 1997
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
and 20 more in the library