5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice.
Sarah J Jefferson, Ian Gregg, Mark Dibbs, Clara Liao, Hao Wu, Pasha A Davoudian, Samuel C Woodburn, Patrick H Wehrle, Jeffrey S Sprouse, Alexander M Sherwood, Alfred P Kaye, Christopher Pittenger, Alex C Kwan
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology August 1, 2023 DOI: 10.1038/s41386-023-01572-w via PubMed
Summary
AI-generated from the abstract5-MeO-DMT, a short-acting psychedelic, produces a dose-dependent increase in head-twitch response in mice that is shorter in duration than psilocybin at all doses tested. It also substantially suppresses social ultrasonic vocalizations during mating behavior. The compound causes long-lasting increases in dendritic spine density in the mouse medial frontal cortex, driven by an elevated rate of spine formation, but unlike psilocybin, it does not affect the size of dendritic spines. These findings reveal behavioral and neural mechanisms of 5-MeO-DMT, highlighting similarities and differences with psilocybin.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 5-MeO-DMT psilocybin |
| Topics | Neuroplasticity |
| Keywords | Neuroscience Psychedelics Behavioral science Mental health |
| Citations | 57 |
| Key finding | 5-MeO-DMT induces a shorter-duration head-twitch response than psilocybin, suppresses mating-related ultrasonic vocalizations, and increases dendritic spine density in the medial frontal cortex through elevated spine formation without altering spine size. |
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.