RT Journal Article
SR Electronic
T1 Microtubule-Stabilizer Epothilone B Delays Anesthetic-Induced Unconsciousness in Rats
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0291-24.2024
DO 10.1523/ENEURO.0291-24.2024
VO 11
IS 8
A1 Khan, Sana
A1 Huang, Yixiang
A1 Timuçin, Derin
A1 Bailey, Shantelle
A1 Lee, Sophia
A1 Lopes, Jessica
A1 Gaunce, Emeline
A1 Mosberger, Jasmine
A1 Zhan, Michelle
A1 Abdelrahman, Bothina
A1 Zeng, Xiran
A1 Wiest, Michael C.
YR 2024
UL http://www.eneuro.org/content/11/8/ENEURO.0291-24.2024.abstract
AB Volatile anesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins. Anesthetic gases including isoflurane bind to cytoskeletal microtubules (MTs) and dampen their quantum optical effects, potentially contributing to causing unconsciousness. This possibility is supported by the finding that taxane chemotherapy consisting of MT-stabilizing drugs reduces the effectiveness of anesthesia during surgery in human cancer patients. In order to experimentally assess the contribution of MTs as functionally relevant targets of volatile anesthetics, we measured latencies to loss of righting reflex (LORR) under 4% isoflurane in male rats injected subcutaneously with vehicle or 0.75 mg/kg of the brain-penetrant MT–stabilizing drug epothilone B (epoB). EpoB-treated rats took an average of 69 s longer to become unconscious as measured by latency to LORR. This was a statistically significant difference corresponding to a standardized mean difference (Cohen's d) of 1.9, indicating a “large” normalized effect size. The effect could not be accounted for by tolerance from repeated exposure to isoflurane. Our results suggest that binding of the anesthetic gas isoflurane to MTs causes unconsciousness and loss of purposeful behavior in rats (and presumably humans and other animals). This finding is predicted by models that posit consciousness as a property of a quantum physical state of neural MTs.