5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – August 01, 2023
Source: PubMed
Summary
A naturally-occurring compound found in some toads shows promise in rapidly reshaping brain connections. This powerful psychedelic, when administered to mice, quickly altered their social behaviors and increased neural connectivity in brain regions linked to emotional processing. The compound's effects were faster-acting than similar substances, with lasting positive changes in brain structure, particularly in the formation of new neural connections in the frontal cortex. These findings point to potential therapeutic applications where rapid intervention is beneficial.
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 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.