Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice.

Autor: Nogueira M; Neurodynamics Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Hearing and Neuronal Activity Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Ferreira Golbert DC; Neurodynamics Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Sleep, Dreams and Memory Laboratory, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Menezes R; Automation and Robotics Laboratory, School of Science and Technology, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Nóbrega de Almeida R; Laboratory of Hormone Measurement, Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Galvão-Coelho NL; Laboratory of Hormone Measurement, Department of Physiology and Behavior, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Siroky AN; Department of Statistics, Exact and Earth Sciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Lima TZ; Hearing and Neuronal Activity Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil.; Department of Statistics, Exact and Earth Sciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Maia H; Automation and Robotics Laboratory, School of Science and Technology, Federal University of Rio Grande do Norte, Natal, RN, Brazil., Leão KE; Hearing and Neuronal Activity Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil. katarina.leao@ufrn.br., Leão RN; Neurodynamics Lab, Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Jul 05. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1038/s41380-024-02655-w
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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