Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice.
Margareth Nogueira, Daiane C Ferreira Golbert, Richardson Menezes, Raíssa Nóbrega de Almeida, Nicole L Galvão-Coelho, Andressa N Siroky, Thiago Z Lima, Helton Maia, Katarina E Leão, Richardson N Leão
Molecular psychiatry January 1, 2025 DOI: 10.1038/s41380-024-02655-w via PubMed
Summary
AI-generated from the abstractA single dose of the short-acting psychedelic 5-MeO-DMT alters expression of genes related to plasticity and neuronal activity in specific brain regions of mice, including the anterior cingulate cortex, basolateral amygdala, and ventral hippocampus. Immediate early genes Arc and Zif268 changed within hours, while TRIP8b, a modulator of neuronal activity, increased in the ventral hippocampus after five days. Behaviorally, 5-MeO-DMT produced mixed anxiety-reducing and anxiety-increasing effects in standard tests, but mice pre-treated with the compound and then exposed to acute stress showed lower corticosterone levels and strong anxiety-reducing effects. The findings suggest molecular pathways through which 5-MeO-DMT may produce anxiolytic effects.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 5-MeO-DMT |
| Dose | single dose |
| Duration | 1 hour, 5 hours, or 5 days |
| Keywords | Neuroscience Psychopharmacology Anxiety research Natural compounds |
| Citations | 18 |
| Key finding | 5-MeO-DMT altered gene expression in brain regions linked to anxiety and, in mice subjected to acute stress, reduced corticosterone levels and produced robust anxiolytic effects. |
Abstract
Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are suggested to have plasticity-inducing action. However, a comprehensive mechanism of action is still lacking. Here, we investigated how a single dose of the short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) acts on gene expression from microdissected brain regions (anterior cingulate cortex - ACC; basolateral amygdala - BLA; ventral hippocampus CA1 region - vCA1 and dentate gyrus-DG) of naive and stressed mice. Specifically, we compared gene expression of Arc, Zif268, BDNF, CREB, mTORC1, NR2A, TRIP8b, and NFkB in mice injected with 5-MeO-DMT or saline at different time points (1 h, 5 h, or 5 days prior). 5-MeO-DMT altered mRNA expression of immediate early genes Arc and ZiF268 in the ACC, BLA, and vCA1, while NR2A expression was decreased after 5 h in the vCA1. We also found a long-term increase in TRIP8b, a gene related to the modulation of neuronal activity, in the vCA1 after 5 days. Behaviorally, 5-MeO-DMT treated mice showed mixed anxiolytic and anxiogenic effects in the elevated plus maze and open field test 24 h or 5 days after treatment. However, pre-treated mice subjected to acute stress showed both lower corticosterone levels and robust anxiolytic effects of 5-MeO-DMT administration. Together, our findings provide insights into the molecular actions of 5-MeO-DMT in the brain related to anxiolytic effects of behavior.