Effects of ketamine and propofol on muscarinic plateau potentials in rat neocortical pyramidal cells.
Anne S. Fleiner, Daniel Kolnier, Nicholas Hagger-Vaughan, Johan Ræder, Johan F. Storm
PLoS One 2025 DOI: 10.1371/journal.pone.0316262 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Rat medial prefrontal cortex slices |
| Interventions | Propofol Ketamine Muscarine |
| Dose | 3 μM propofol, 20 μM ketamine, 100 μM ketamine |
| Duration | 2 hours of pre-incubation |
| Topics | Esketamine Ketamine |
| Keywords | Anesthesia Brain activity Sleep medicine Drug effects |
| Citations | 1 |
| Key findings | Propofol reduced muscarine-induced plateau potentials and spiking in rat medial prefrontal cortex pyramidal cells, while low-dose ketamine appeared to enhance them, possibly explaining their different effects on dreaming during anesthesia. |
Abstract
Propofol and ketamine are widely used general anaesthetics, but have different effects on consciousness: propofol gives a deeply unconscious state, with little or no dream reports, whereas vivid dreams are often reported after ketamine anaesthesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, while propofol is a γ-aminobutyric-acid (GABAA) receptor positive allosteric modulator, but these mechanisms do not fully explain how these drugs alter consciousness. Most previous in vitro studies of cellular mechanisms of anaesthetics have used brain slices or neurons in a nearly "comatose" state, because no "arousing" neuromodulators were added. Here we tested mechanisms of anaesthetics in rat medial prefrontal cortex (mPFC) slices after bath-applying the cholinergic agonist muscarine to partly mimic an "aroused-like" state, using whole-cell patch-clamp recordings from layer 2/3 pyramidal cells (L2/3PCs). According to leading theories of access consciousness and working memory, L2/3PCs are particularly important for these cognitive functions. We found that muscarine induced long-lasting depolarising plateau potentials (PPs) and spiking following brief depolarising current injections in the L2/3PCs. After 2 hours of pre-incubation with ketamine or propofol, the muscarine-induced PPs were altered in seemingly different ways: 3 μM propofol reduced the PPs and (significantly) spiking, whereas 20 μM ketamine seemed to enhance PPs and spiking (non-significantly). Brief wash-in of these drug concentrations failed to induce such effects, probably due to insufficient equilibration by diffusion in the slices. In contrast, pre-incubation with a high dose (100 μM) of ketamine suppressed the PPs and spiking. We discuss whether the apparently different effects on PPs may possibly be related to contrasting clinical effects: ketamine causing atypical anaesthesia with vivid, "psychedelic" dreaming while propofol causes less dreaming.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cites 21
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior Science Translational Medicine August 14, 2013
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence Journal of Neuroscience October 4, 2017
and 16 more in the library