Ketamine: differential neurophysiological dynamics in functional networks in the rat brain.
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Translational Psychiatry September 19, 2017 DOI: 10.1038/tp.2017.198 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Dose | 2.5, 5 and 10 mg kg-1 |
| Duration | Acute and chronic subcutaneous administration |
| Measures | coherence, phase-amplitude cross-frequency coupling, mismatch negativity-like (MMN) component of event-related brain potentials (ERPs), event-related oscillations (EROs), locomotor activity (LMA) |
| Topics | Esketamine Ketamine |
| Key findings | Acute and chronic subcutaneous ketamine produced opposing effects on brain network activity in rats: acute dosing increased gamma coherence, altered theta-gamma coupling, and enhanced MMN and evoked gamma responses, while chronic dosing reduced gamma oscillations and coherence, shifted activity toward slow alpha, and decreased MMN response. The authors propose these changes reflect altered NMDAR-GABAergic signaling and contend that intermittent dosing may better preserve network integrity for long-term therapeutic effects. |
Abstract
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2.5, 5 and 10 mg kg-1) on sleep-wake cycle, multichannels network interactions assessed by coherence and phase-amplitude cross-frequency coupling, locomotor activity (LMA), cognitive information processing as reflected by the mismatch negativity-like (MMN) component of event-related brain potentials (ERPs). Acute ketamine elicited a short, lasting inhibition of rapid eye movement (REM) sleep, increased coherence in higher gamma frequency oscillations independent of LMA, altered theta-gamma phase-amplitude coupling, increased MMN peak-amplitude response and evoked higher gamma oscillations. In contrast, chronic ketamine reduced large-scale communication among cortical regions by decreasing oscillations and coherent activity in the gamma frequency range, shifted networks activity towards slow alpha rhythm, decreased MMN peak response and enhanced aberrant higher gamma neuronal network oscillations. Altogether, our data show that acute and chronic ketamine elicited differential changes in network connectivity, ERPs and event-related oscillations (EROs), supporting possible underlying alterations in NMDAR-GABAergic signaling. The findings underscore the relevance of intermittent dosing of ketamine to accurately maintain the functional integrity of neuronal networks for long-term plastic changes and therapeutic effect.
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 19
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms PLoS Computational Biology August 18, 2021
- (S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats The International Journal of Neuropsychopharmacology September 25, 2023
- EEG Gamma Band Alterations and REM-like Traits Underpin the Acute Effect of the Atypical Psychedelic Ibogaine in the Rat. ACS Pharmacology & Translational Science April 9, 2021
- Ketamine supresses REM sleep and markedly increases EEG gamma oscillations in the Wistar Kyoto rat model of treatment-resistant depression. Behavioural Brain Research May 1, 2023
and 14 more in the library
Cites 14
- Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance Neuroimage August 19, 2011
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects Molecular Psychiatry October 15, 2013
- Ketamine alters oscillatory coupling in the hippocampus Scientific Reports August 2, 2013
and 9 more in the library