Psychedelic-mediated Reversal of General Anesthesia and Restoration of Brain Dynamics in Rat
Emma R. Huels, Nicholas Kolbman, Christopher W Fields, Amanda Nelson, Hazel Jackson, Tiecheng Liu, George A. Mashour, Dinesh Pal
bioRxiv Preprint Server January 22, 2025 preprint DOI: 10.1101/2025.01.22.632279 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Rats |
| Interventions | DOI propofol isoflurane volinanserin lisuride |
| Citations | 4 |
| Key findings | Intravenous administration of DOI in rats under general anesthesia induced wakefulness and restored brain dynamics despite ongoing delivery of propofol or isoflurane. |
Abstract
Serotonergic psychedelics enhance neurophysiological complexity and the repertoire of brain states, whereas general anesthetics produce opposite effects. Serotonergic psychedelics are also known to increase wakefulness and reduce sleep time in rodents. Therefore, we hypothesized that 2,5-dimethoxy-4-iodopamphetamine (DOI), a serotonergic psychedelic, will reverse general anesthesia and restore neurophysiological conditions associated with normal wakefulness. We demonstrate that intravenous administration of DOI in rats under general anesthesia induced wakefulness despite ongoing delivery of the anesthetics, propofol or isoflurane. Behavioral arousal was accompanied by recovery of directional and non-directional high gamma (125-165Hz) functional connectivity and restoration of functional brain network structure. These behavioral and neurophysiological effects were blocked by a 5-HT2A antagonist, volinanserin. Intravenous administration of a non-psychedelic 5-HT2A agonist, lisuride, failed to restore wakefulness or brain dynamics in anesthetized rats. To our knowledge, these results provide the first evidence of psychedelic-mediated reversal of general anesthesia and concurrent restoration of brain dynamics associated with normal wakefulness.