5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Jefferson, S. J.; Gregg, I.; Dibbs, M.; Liao, C.; Wu, H.; Davoudian, P. A.; Sprouse, J. S.; Sherwood, A. M.; Kaye, A. P.; Pittenger, C.; Kwan, A. C.

doi:10.1101/2022.11.03.515044

bioRxiv · 10.1101/2022.11.03.515044

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Jefferson, S. J.·Gregg, I.·Dibbs, M.·Liao, C.·Wu, H.·Davoudian, P. A.·Sprouse, J. S.·Sherwood, A. M.·Kaye, A. P.·Pittenger, C.·Kwan, A. C.

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Abstract

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early clinical studies. However relatively little is known about the behavioral effects and neural mechanisms of 5-MeO-DMT in animal models. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.

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Jefferson, S. J., Gregg, I., Dibbs, M., Liao, C., Wu, H., Davoudian, P. A., Sprouse, J. S., Sherwood, A. M., Kaye, A. P., Pittenger, C., Kwan, A. C.. 2022-11-03. 5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice. https://doi.org/10.1101/2022.11.03.515044

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