Neuronal glutamatergic changes and peripheral markers of cytoskeleton dynamics change synchronically 24 h after sub-anaesthetic dose of ketamine in healthy subjects.
Lejla Colic, Conor McDonnell, Meng Li, Marie Woelfer, Thomas Liebe, Moritz Kretzschmar, Oliver Speck, Björn H Schott, Massimiliano Bianchi, Martin Walter
Behavioural Brain Research February 1, 2019 DOI: 10.1016/j.bbr.2018.10.021 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Healthy controls (age 25.89 ± 5.29 years, 33 women) |
| Interventions | Ketamine Saline |
| Dose | 0.5 mg/kg |
| Duration | 24-hour follow-up after infusion |
| Measures | Acet-Tub/TRF via infrared western blotting, Glu/Cr via proton magnetic resonance spectroscopy (1H-MRS) |
| Topics | Ketamine Esketamine |
| Keywords | Acet-tub Blood markers Gender specificity Glutamatergic system |
| Key findings | Ketamine increased pgACC Glu/Cr at 24 hours in both sexes, while Acet-Tub/TRF rose only in women. Ketamine-induced Glu/Cr change correlated negatively with Acet-Tub/TRF in the ketamine group (r = -0.464), a correlation significant only among women, suggesting a sex-specific temporal link between central glutamatergic effects and peripheral cytoskeleton markers. |
Abstract
Ketamine acts as a rapid-acting antidepressant by restoring glutamatergic deficits and activating synaptic plasticity processes, with peak activity 24 h after infusion. Microtubule dynamics are known to play a key role in modulation of cytoskeleton and synaptic plasticity, as well as in signalling events in peripheral blood cells. Here, we correlated ketamine-induced change in glutamate/creatinine (Glu/Cr) levels in the pregenual anterior cingulate cortex (pgACC) with peripheral markers of microtubule dynamics, namely acetylated α-tubulin (Acet-Tub), with particular attention to gender specificity. Eighty healthy controls (age = 25.89 ± 5.29, 33 women) were administered intravenous infusion of either ketamine (0.5 mg/kg) or placebo (saline). Blood samples were obtained at baseline and 24 h after infusion and plasma levels of Acet-Tub and transferrin (TRF; loading control) were measured via infrared western blotting. Glu/Cr levels were measured via high-field (7 T) proton magnetic resonance spectroscopy [1H-MRS] in the pgACC at the same time points. Gender differences were observed in baseline Acet-Tub/TRF levels (p < 0.001), and an interaction of time by treatment by gender (F = 5.13, p = 0.027) was found, with a significant increase in Acet-Tub/TRF for ketamine group in females only (p = 0.038). Ketamine-induced gender-independent Glu/Cr changes at 24 h (F(1, 69) = 4.08, p = 0.047), and changes in the pgACC were negatively correlated with the Acet-Tub/TRF expression (r= -0.464, p = 0.010) in the ketamine group, in which, separated by sex, only women showed significant correlation. Our findings indicate a temporal association between changes in central ketamine-induced glutamatergic effects and peripheral markers of cytoskeleton reorganization, particularly in females.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 8
- An exploration of the relationships between the effects of psilocybin on behavior, 5-HT 2A receptor occupancy, and neuroplastic effects in mice Journal of Psychopharmacology January 6, 2026
- Sex and Age Differences in Ketamine Efficacy and Safety in Chronic Pain Alleviation. Journal of Clinical Medicine June 16, 2025
- Modulation of Magnetic Resonance Spectroscopy Levels of Glutamate and GABA by Ketamine in Treatment-Resistant Depression. Journal of Neuroscience Research 2026
- Ketamine administration reduced conditioned defensive behaviour and upregulated protein expression associated with neuroplasticity in a planarian model of aversive memory reactivation. Progress in neuro-psychopharmacology & biological psychiatry October 17, 2026
- Neurometabolite changes in response to antidepressant medication: A systematic review of 1H-MRS findings. NeuroImage: Clinical 2023
and 3 more in the library
Cites 13
- 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
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Translational Psychiatry March 21, 2017
- Longitudinal Effects of Ketamine on Dendritic ArchitectureIn Vivoin the Mouse Medial Frontal Cortex eNeuro March 1, 2016
and 8 more in the library