Psychedelic-mediated Reversal of General Anesthesia and Restoration of Brain Dynamics in Rat
bioRxiv – January 22, 2025
Source: medRxiv/bioRxiv/arXiv
Summary
Remarkably, a serotonergic psychedelic can awaken anesthetized rats, restoring brain activity linked to alertness. Researchers found that administering DOI led to wakefulness even under anesthesia, enhancing brain connectivity. This breakthrough suggests psychedelics may uniquely reverse anesthesia effects and revive normal brain function.
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.