Effects of subanesthetic intravenous ketamine infusion on neuroplasticity-related proteins in the prefrontal cortex, amygdala, and hippocampus of Sprague-Dawley rats
Michael Zhang, Kennett D. Radford, Mercedes Y. Driscoll, Salsabila Purnomo, Jean Kim, Kwang H. Choi
IBRO Reports January 16, 2019 DOI: 10.1016/j.ibror.2019.01.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Intervention | Ketamine infusion |
| Dose | 40 mg/kg/2 h or 10 mg/kg/2 h |
| Duration | 2-hour infusion, tissue collected 2 hours after infusion |
| Topics | Esketamine Ketamine Neuroplasticity |
| Citations | 34 |
| Key findings | Ketamine produces dose-dependent and brain region-specific effects on c-Fos, BDNF, and pERK protein levels in rats. |
Abstract
Ketamine, a multimodal dissociative anesthetic, is a powerful analgesic administered following trauma due to its hemodynamic and respiratory stability. However, ketamine can cause hallucination and dissociation which may adversely impact traumatic memory after an injury. The effects of ketamine on proteins implicated in neural plasticity are unclear due to different doses, routes, and timing of drug administration in previous studies. Here, we investigated the effects of a single intravenous (IV) ketamine infusion on protein levels in three brain regions of rats. Adult male Sprague-Dawley rats with indwelling IV catheters underwent an auditory fear conditioning (three pairings of tone and mild footshock 0.8 mA, 0.5 s) and received a high dose of IV ketamine (0 or 40 mg/kg/2 h) infusion (Experiment 1). In a follow-up study, animals received a low dose of IV ketamine (0 or 10 mg/kg/2 h) infusion (Experiment 2). Two hours after the infusion, brain tissue from the medial prefrontal cortex (mPFC), hippocampus, and amygdala were collected for western blot analyses. Protein levels of a transcription factor (c-Fos), brain-derived neurotrophic factor (BDNF), and phosphorylated extracellular signal-regulated kinase (pERK) were quantified in these regions. The 40 mg/kg ketamine infusion increased c-Fos levels in the mPFC and amygdala as well as pERK levels in the mPFC and hippocampus. The 10 mg/kg ketamine infusion increased BDNF levels in the amygdala, but decreased pERK levels in the mPFC and hippocampus. These findings suggest that a clinically relevant route of ketamine administration produces dose-dependent and brain region-specific effects on proteins involved in neuroplasticity.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 13
- A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain International Journal of Molecular Sciences January 15, 2021
- Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers ACS Pharmacology & Translational Science August 31, 2020
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD. Psychopharmacology June 1, 2025
- Temporal dynamics of BDNF signaling recruitment in the rat prefrontal cortex and hippocampus following a single infusion of a translational dose of ketamine Neuropharmacology October 17, 2023
- Ketamine's Amelioration of Fear Extinction in Adolescent Male Mice Is Associated with the Activation of the Hippocampal Akt-mTOR-GluA1 Pathway. Pharmaceuticals May 22, 2024
and 8 more in the library
Cites 9
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Electroencephalographic Spectral and Coherence Analysis of Ketamine in Rats: Correlation with Behavioral Effects and Pharmacokinetics Neuropsychobiology 2011
- Ketamine-induced hypnosis and neuroplasticity in mice is associated with disrupted p-MEK/p-ERK sequential activation and sustained upregulation of survival p-FADD in brain cortex: Involvement of GABAA receptor. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 10, 2018
- Acute low-dose ketamine produces a rapid and robust increase in plasma BDNF without altering brain BDNF concentrations. Drug delivery and translational research June 2018
- Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression. Behavioural Brain Research June 6, 2011
and 4 more in the library