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

Apr 4, 2023Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

5-MeO-DMT changes natural behaviors and encourages brain cell growth in mice

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Abstract

5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin.

5-MeO-DMT significantly suppresses social ultrasonic vocalizations during mating behavior.
The compound leads to long-lasting increases in dendritic spine density in the mouse medial frontal cortex.
This increase in spine density is associated with a higher rate of spine formation.
In contrast to psilocybin, 5-MeO-DMT does not affect the size of dendritic spines.

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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 phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. 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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5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice

Abstract

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