ABSTRACT NUMBER: ESOC2026YS125 DIMETHYLTRYPTAMINE INHIBITS SPREADING DEPOLARISATION IN BRAIN SLICES OF SIGMA-1 RECEPTORKNOCKOUT MICE
Anna Zsigmond, Rita Frank, Botond Eröss, Andrea Fekete, Ádám Hosszú, Ákos Menyhárt, Sándor Nardai, Eszter Farkas
European Stroke Journal May 1, 2026 DOI: 10.1093/esj/aakag023.1209 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study using brain slices Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Wild-type C57BL/6 and S1R receptor knockout mice |
| Intervention | Dimethyltryptamine (DMT) |
| Dose | 20 μM |
| Topics | 5-MeO-DMT DMT |
| Keywords | Neuroprotection Agonist Neun Depolarization Receptor Knockout mouse Stroke engine Pharmacology Viability assay Biophysics Neuron Ischemia |
| Key findings | DMT reduced spreading depolarization measures more effectively in sigma-1 receptor knockout mice than in wild-type, suggesting neuroprotection involves aminergic receptors. |
Abstract
Abstract Background and aims Spreading depolarizations (SDs) exacerbate neuronal injury during acute ischemic stroke (AIS). The sigma-1 receptor (S1R) agonist dimethyltryptamine (DMT) reduces cellular damage, inhibits SDs, and enhances neuronal survival in rodent models of AIS. Although DMT primarily acts on S1R, it also binds to aminergic receptors. Therefore, we aimed to determine the S1R-mediated neuroprotective effects of DMT.
Methods: 350-μm-thick brain slices were prepared from wild-type C57BL/6 (WT) and S1R receptor knockout (S1R-KO) mice (n=12). To model acute ischemic stroke (AIS), a medium of reduced glucose content was applied, and SDs were induced by hypoxia. SDs were recorded using intrinsic optical signal (white-light reflectance) imaging and local field potential recordings. Brain slices were incubated in solutions containing DMT (20 μM) or its vehicle. Neuronal viability was assessed using NeuN immunohistochemistry.
Results: DMT reduced the cortical area affected by SDs in both WT and S1R-KO animals (53.3±21.6% vs. 65.7±13.8% and 42.1±11.2% vs. 61.0±12.7%; WT+DMT vs. WT and S1R-KO+DMT vs. S1R-KO). Furthermore, DMT reduced the area under the curve of SDs (299.9±148.0 vs. 543.3±270.5 mV·s, S1R-KO+DMT vs. S1R-KO) and their propagation velocity (2.6±1.0 vs. 3.8±1.8 mm/min) in S1R KO animals only. NeuN-positive cell number tended to increase following DMT treatment. Contrary to our expectations, these results demonstrate that DMT is more effective in S1R-KO than in WT animals, suggesting that its neuroprotective effects are mediated by aminergic receptors in addition to S1R activation. These findings support the potential adjuvant use of DMT in the treatment of AIS. Conflict of interest
Funding: EU H2020-HCEMM (No. 739593), NKFIH (No. K146725), The Hungarian Brain Research Program 3.0. to E.F. and Á.M., National Research, Development and Innovation Office of Hungary (PD137565) to N.S.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |